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Expression and localization of acetylcholinesterase at the neuromuscular junction

Journal of Neurocytology volume 32, pages 743–766 (2003)Cite this article

Abstract

Acetylcholinesterase (AChE) was the first identified synaptic component, characterized by its catalytic affinity for choline esters, and for a long time provided the conceptual scaffold for studies of the neuromuscular junction (NMJ). AChE was the first protein localized to the NMJ, in the 1930s, and its local expression shown to be regulated by the motoneuron in 1937. By the late 1940s a histochemical procedure was developed to visualize the enzyme at synapses, opening up a new era in the study of synaptic structure and function. This enzyme was also the first synaptic component to be purified, quantified, and later crystalized for structural and functional studies. Thus, historically, AChE has played a pivotal role in our understanding of NMJ development and function.

AChE occurs in multiple oligomeric forms differing in their hydrophobic character and association with non-catalytic subunits that act as targeting sequences to insure correct localization at the cellular level. The predominant, if not unique, form of the enzyme responsible for terminating neuromuscular transmission is the collagen-tailed form of the enzyme attached to the synaptic basal lamina. This very large protein consists of three catalytic tetramers covalently linked to the three-stranded collagen-like tail (ColQ). The transcripts encoding AChE in muscle are preferentially expressed at sites of nerve-muscle contact and the AChE locally synthesized and assembled. Once externalized, the enzyme appears to be localized through interactions with the proteoglycan perlecan and subsequently covalently attached to the synaptic extracellular matrix. Thus a hierarchical series of events involving localized transcription and translation of the catalytic and non-catalytic subunits, localized assembly and secretion, and finally localized attachment to elements of the extracellular matrix insures that the enzyme is targeted to the correct location.

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References

  • ADAMS, M. E., KRAMARCY, N. R., KRALL, S. P., ROSSI, S. G., ROTUNDO, R. L., SEALOCK, R. & FROEHNER, S. C. (2000) Absence of ?-syntrophin leads to structurally aberrant neuromuscular synapses deficient in utrophin. J. Cell Biol. 150(6), 138–1397.

    PubMed  Google Scholar 

  • ANGLISTER, L. (1991) Acetylcholinesterase from the motor nerve terminal accumulates on the synaptic basal lamina of the myofiber. J. Cell Biol. 115, 75–764.

    PubMed  Google Scholar 

  • ANGLISTER, L., EICHLER, J., SZABO, M., HAESAERT, B. & SALPETER, M. M. (1998) 125I-labeled fasciculin 2: A new tool for quantitation of acetylcholinesterase densities at synaptic site by EM-autoradiography. J. of Neuroscience Methods 81, 6–71.

    Google Scholar 

  • ANGLISTER, L., MCMAHAN, U. J. & MARSHALL, R. M. (1985) Basal lamina direct acetylcholinesterase accumulation at synaptic sites in regenerating muscle. J. Cell Biol. 101, 73–743.

    PubMed  Google Scholar 

  • ANGLISTER, L. & SILMAN, I. (1978) Molecular structure of elongated forms of electric eel acetylcholinesterase. J. Mol. Biol. 125, 29–311.

    PubMed  Google Scholar 

  • ANGLISTER, L., STILES, J. R. & SALPETER, M. M. (1994) Acetylcholinesterase density and turnover number at frog neuromuscular junctions, with modeling of their role in synaptic function. Neuron 12, 78–794.

    PubMed  Google Scholar 

  • APEL, E. D., ROBERDS, S. L., CAMPBELL, K. P. & MERLIE, J. P. (1995) Rapsyn may functin as a link between the acetylcholine receptor and the agrin-binding dystrophin-associated glycoprotein complex. Neuron 15, 11–126.

    PubMed  Google Scholar 

  • ARIKAWA-HIRASAWA, E., ROSSI, S. G., ROTUNDO, R. L. & YAMADA, Y. (2002) Absence of acetylcholinesterase at the neuromuscular junctions of perlecan-null mice. Nat. Neurosci. 5, 11–123.

    PubMed  Google Scholar 

  • ARPAGAUS, M., KOTT, M., VATSIS, K. P., BARTELS, C. F., LA DU, B. N. & LOCKRIDGE, O. (1990) Structure of the gene for human butyrylcholinesterase. Evidence for a single copy. Biochemistry 29, 12–131.

    PubMed  Google Scholar 

  • ATANASOVA, E., CHIAPPA, S., WIEBEN, E. & BRIMIJOIN, S. (1999) Novel messenger RNA and alternative promoter for murine acetylcholinesterase. J. Biol. Chem. 274, 2107–21084.

    PubMed  Google Scholar 

  • AZIZ-ALOYA, R., STERNFELD, M. & SOREQ, H. (1993) Promoter elements and alternative splicing in the human ACHE gene. Prog. Brain Res. 98, 14–153.

    PubMed  Google Scholar 

  • BETZ, W. & SAKMANN, B. (1971) ”Distinction” of frog neuromuscular synapses by treatment with proteolytic enzymes. Nature New Bio. 232, 9–95.

    Google Scholar 

  • BETZ, W. & SAKMANN, B. (1973) Effects of proteolytic enzymes on funtion and structure of frog neuromuscular junctions. J. Physiol. Lon. 230, 67–688.

    Google Scholar 

  • BON, S., CARTAUD, J. & MASSOULIÉ, J. (1978) The dependence of Acetylcholinesterase aggregation at low ionic strength upon a polyanionic component. Eur. J. Biochem. 85, –14.

    PubMed  Google Scholar 

  • BON, S., COUSSEN, F. & MASSOULIÉ, J. (1997) Quaternary associations of acetylcholinesteraseII. The polyproline attachment domain of the collagen-tail. The Journal of Bio. Chem. 272(5), 301–3021.

    Google Scholar 

  • BON, S. & MASSOULIÉ, J. (1997) Quaternary associations of acetylcholinesterase I. Oligomeric associations of T subunits with without the amino-terminal domain of the collagen-tail. The Journal of Bio. Chem. 272(5), 300– 3015.

    Google Scholar 

  • BOUDREAU-LARIVIERE, C., CHAN, R. Y., WU, J. & JASMIN, B. J. (2000) Molecular mechanisms underlying the activity-linked alterations in acetylcholinesterase mRNAs in developing versus adult rat skeletal muscles. J. Neurochem. 74, 225–2258.

    PubMed  Google Scholar 

  • BOUDREAU-LARIVIERE, C. & JASMIN, B. J. (1999) Calcitonin gene-related peptide decreases expression of acetylcholinesterase in mammalian myotubes. FEBS Letter 444, 2–26.

    Google Scholar 

  • BOURNE, Y., TAYLOR, P. & MARCHOT, P. (1995) Acetylcholinesterase inhibition by fasciculin: Crystal structure of the complex. Cell 83, 50–512.

    PubMed  Google Scholar 

  • BOWE, M. A., DEYST, K. A., LESZYK, J. D. & FALLON, J. R. (1994) Identification and purification of an agrin receptor from torpedo postsynaptic membranes: A heteromeric complex related to the dystroglycans. Neuron 12, 117–1180.

    PubMed  Google Scholar 

  • BOWE, M. A. & FALLON, J. R. (1995) The role of agrin in synapse formation. Annu. Rev. Neurosci. 18, 44–462.

    PubMed  Google Scholar 

  • BRANDAN, E. & INESTROSA, N. C. (1984) Binding of the asymmetric forms of acetylcholinesterase to heparin. Biochem. J. 221, 41–422.

    PubMed  Google Scholar 

  • BRIGUET, A. & RUEGG, M. A. (2000) The Ets transcription factor GABP is required for postsynaptic differentiation in vivo. J. Neurosci. 20, 598–5996.

    PubMed  Google Scholar 

  • BRIMIJOIN, S. (1979) Axonal transport and subcellular distribution of molecular forms of acetylcholinesterase in rabbit sciatic nerve. Mol. Pharmacol. 15, 64–648.

    PubMed  Google Scholar 

  • BROCKMAN, S. K., PRZYBYLSKI, R. J. & YOUNKIN, S. G. (1982) Cellular localization of the molecular forms of acetylcholinesterase in cultured embroyonic rat myotubes. J. Neurosc. 2, 177–1785.

    Google Scholar 

  • BROCKMAN, S. K., USIAK, M. F. & YOUNKIN, S. G. (1986) Assembly of monomeric acetylcholinesterase into tetrameric and asymmetric forms. J. Biol. Chem. 261, 120–1207.

    PubMed  Google Scholar 

  • BURDEN, S. J. (1993) Synapse-specific gene expression. Trends Genet. 9, 1–16.

    PubMed  Google Scholar 

  • BURDEN, S. J. (1998) The formation of neuromuscular synapses. Genes Dev. 12, 13–148.

    PubMed  Google Scholar 

  • CAMPANELLI, J. T., ROBERDS, S. L., CAMPBELL, K. P. & SCHELLER, R. H. (1994) A role for dystrophinassociated glycoproteins and utrophin in agrin-induced AChR clustering. Cell 77, 66–674.

    PubMed  Google Scholar 

  • CASANUEVA, O. I., GARCIA-HUIDOBRO, T., CAMPOS, E. O., ALDUNATE, R., GARRIDO, J. & INESTROSA, N. C. (1998) A major portion of synaptic basal lamina acetylcholinesterase is detached by high salt-and heparin-containing buffers from rat diaphragm muscle and Torpedo electric organ. J. Biol. Chem. 273, 425–4265.

    PubMed  Google Scholar 

  • CHAHINE, K. G., BARACCHINI, E. & GOLDMAN, D. (1993) Coupling muscle electrical activity to gene expression via a cAMP-dependent second messenger system. The Journal of Bio. Chem. 268, 289–2898.

    Google Scholar 

  • CHAN, R. Y., BOUDREAU-LARIVIERE, C., ANGUS, L. M., MANKAL, F. A. & JASMIN, B. J. (1999) An intronic enhancer containing an N-box motif is required for synapse-and tissue-specific expression of the acetylcholinesterase gene in skeletal muscle fibers. Proc. Natl. Acad. Sci. USA 96, 462–4632.

    PubMed  Google Scholar 

  • CHATEL, J. M., GRASSI, J., FROBERT, Y., MASSOULIÉ, J. & VALLETTE, F. M. (1993) Existence of an inactive pool of acetylcholinesterase in chicken brain. Proc. Natl. Acad. Sci. USA 90(6), 247–2480.

    PubMed  Google Scholar 

  • CHITLARU, T., KRONMAN, C., ZEEVI, M., KAM, M., HAREL, A., ORDENTLICH, A., VELAN, B. & SHAFFERMAN, A. (1998) Modulation of circulatory residence of recombinant acetylcholinesterase through biochemical or genetic manipulation of sialylation levels. Biochem. J. 336(Pt 3), 64–658.

    PubMed  Google Scholar 

  • CHOI, R. C. Y., MAN, M. L. S., LING, K. K. Y., IP, N. Y., SIMON, J., BARNARD, E. A. & TSIM, K. W. K. (2001a) Expression of the P2Y1 nucleotide receptor in chick muscle: Its functional role in the regulation of acetylcholinesterase and acetylcholine receptors. J. of Neuroscience 21(23), 922–9234.

    Google Scholar 

  • CHOI, R. C. Y., SIOW, N. L., ZHU, S. Q., WAN, D. C. C., WONG, Y. H. & TSIM, K. W. K. (2001b) The cyclic AMP-mediated expression of acetylcholinesterase in myotubes shows contrasting activation and repression between avian and mammalian enzymes. Molecular and Cellular Neuroscience 17, 73–745.

    PubMed  Google Scholar 

  • CHOI, R. C. Y., YUNG, L. Y., DONG, T. T. X., WAN, D. C. C., WONG, Y. H. & TSIM, K. W. K. (1998) The calcitonin gene-related peptide-induced acetylcholinesterase synthesis in cultured chick myotubes is mediated by cyclic AMP. J of Neurochemistry 71, 15–160.

    Google Scholar 

  • COHEN, M. W., JACOBSON, C., GODFREY, E., CAMPBELL, K. P. & CARBONETTO, S. (1995) Distribution of alpha-dystroglycan during embryonic nerve-muscle synaptogenesis. J. Cell Biol. 129, 109– 1101.

    PubMed  Google Scholar 

  • COLLINS, P. L. & YOUNKIN, S. G. (1982) Effect of denervation on the molecular forms of acetylcholinesterase in rat diaphram. J. Biol. Chem. 257, 1363–13644.

    PubMed  Google Scholar 

  • COTE, P. D., MOUKHLES, H., LINDENBAUM, M. & CARBONETTO, S. (1999) Chimaeric mice deficient in dystroglycans develop muscular dystrophy and have disrupted myoneural synapses. Nature Genetics 23, 33–342.

    PubMed  Google Scholar 

  • COURAUD, J. Y. & DIGIAMBERARDINO, L. (1980) Axonal transport of the molecular forms of acetylcholinesterase in chick sciatic nerve. J. Neurochem. 35, 105–1066.

    PubMed  Google Scholar 

  • COUTEAUX, R. & NACHMANSOHN, D. (1938) Cholinesterase at the end-plates of voluntary muscle after nerve degeneration. Nature 142, 481 (Ref Type: Generic).

    Google Scholar 

  • DE LA, P. S., CHAUBOURT, E., FABRE, F., POULAS, K., CHAPRON, J., EYMARD, B., TZARTOS, S. & KOENIG, J. (1998) Accumulation of acetylcholine receptors is a necessary condition for normal accumulation of acetylcholinesterase during in vitro neuromuscular synaptogenesis. Eur. J. Neurosci. 10, 163–1643.

    PubMed  Google Scholar 

  • DE LAPORTE, S., VALLETTE, F. M., GRASSI, J., VIGNY, M. & KOENIG, J. (1986) Presynaptic or postsynaptic origin of acetylcholinesterase at neuromuscular junctions? An immunological study in heterologous nervemuscle cultures. Dev. Biol. 116, 6–77.

    PubMed  Google Scholar 

  • DECHIARA, T. M., BOWEN, D. C., VALENZUELA, D. M., SIMMONS, M. V., POUEYMIROU, W. T. THOMAS, S., KINETZ, E., COMPTON, D. L., ROJAS, E., PARK, J. S., SMITH, C., DISTEFANO, P. S., GLASS, D. J., BURDEN, S. J. & YANCOPOULOS, G. D. (1996) The receptor tyrosine kinase MuSK is required for neuromuscular junction formation in vivo. Cell 85, 50–512.

    PubMed  Google Scholar 

  • DEL CASTILLO, J. & KATZ, B. (1955) On the localization of acetylcholine receptors. J. Physiology 128, 15–181.

    Google Scholar 

  • DEPREZ, P. N. & INESTROSA, N. C. (1995) Two heparinbinding domains are present on the collagenic tail of asymmetric acetylcholinesterase. The Journal of Bio. Chem. 270(12), 1104–11046.

    Google Scholar 

  • DIGIAMBERARDINO, L. (1978) Rapid accumulation of high molecular weight acetylcholinesterase in transected sciatic nerve. Nature 271, 17–172.

    PubMed  Google Scholar 

  • DO, T. A., DE LA, P. S. & KOENIG, J. (1984) Simultaneous visualization of acetylcholinesterase activity and acetylcholine receptor clusters at neuromuscular synapses in vivo and in vitro. Biol. Cell 50, 9–102.

    PubMed  Google Scholar 

  • DONGER, C., KREJCI, E., SERRADELL, A. P., EYMARD, B., BON, S., NICOLE, S., CHATEAU, D., GARY, F., FARDEAU, M., MASSOULIÉ, J. & GUICHENEY, P. (1998) Mutation in the human acetylcholinesteraseassociated collagen gene, COLQ, is responsible for congenital myasthenic syndrome with end-plate acetylcholinesterase deficiency (type Ic). Am. J. Hum. Genet. 63, 96–975.

    PubMed  Google Scholar 

  • DOTTI, C. G., PARTON, R. G. & SIMONS, K. (1991) Polarized sorting of glypiated proteins in hippocampal neurons. Nature 349, 15–161.

    PubMed  Google Scholar 

  • DOTTI, C. G. & SIMONS, K. (1990) Polarized sorting of viral glycoproteins to the axon and dendrites of hippocampal neurons in culture. Cell 62, 6–72.

    PubMed  Google Scholar 

  • DUDAI, Y., HERZBERG, M. & SILMAN, I. (1973) Molecular structure of acetylcholinesterase from electric organ tissue of the electric eel. Proc. Natl. Acad. Sci. USA 70, 247–2476.

    PubMed  Google Scholar 

  • DUDAI, Y., SILMAN, I., S HINITZKY, M. & BLUMBERG, S. (1972) Purification by affinity chromatography of the molecular forms of acetylcholinesterase present in fresh electric-organ tissue of electric eel. Proc. Natl. Acad. Sci. USA 69, 240–2403.

    PubMed  Google Scholar 

  • DUVAL, N., MASSOULIÉ, J. & BON, S. (1992) H and T subunits of acetylcholinesterase from Torpedo, expressed in COS cells, generate all types of globular forms. The Journal of Cell Biology 118, 64–653.

    PubMed  Google Scholar 

  • EICHLER, J., SILMAN, I. & ANGLISTER, L. (1992) G2-acetylcholinesterase is presynaptically localized in Torpedo electric organ. J. Neurocytol. 21, 70–716.

    PubMed  Google Scholar 

  • EICHLER, J., SILMAN, I., GENTRY, M. K. & ANGLISTER, L. (1990) Immunocytochemical localization of phosphatidylinositol-anchored acetylcholinesterase in excitable membranes of torpedo ocellata. Molecular Brain Research 8, 21–218.

    PubMed  Google Scholar 

  • EKSTROM, T. J., KLUMP, W. M., GETMAN, D., KARIN, M. & TAYLOR, P. (1993) Promoter elements and transcriptional regulation of the acetylcholinesterase gene. DNA Cell Biol. 12, 6–72.

    PubMed  Google Scholar 

  • ERVASTI, J. M. & CAMPBELL, K. P. (1993) A role for the dystrophin-glycoprotein complex as a transmembrane linker between laminin and actin. The Journal of Cell Biology 122, 80–823.

    PubMed  Google Scholar 

  • FALLON, J. R. & HALL, Z. W. (1994) Building synapses: Agrin and dystroglycan stick together. TINS 17(11), 46–473.

    PubMed  Google Scholar 

  • FENG, G., KREJCI, E., MOLGO, J., CUNNINGHAM, J. M., MASSOULIÉ, J. & SANES, J. R. (1999) Genetic analysis of collagen Q: Roles in acetylcholinesterase and butyrylcholinesterase assembly and in synaptic structure and function. J. Cell Biol. 144, 134–1360.

    PubMed  Google Scholar 

  • FERNANDEZ, H. L. & HODGES-SAVOLA, A. (1996) Physiological regulation of G4 AChE in fast-twitch muscle: Effects of exercise and CGRP. J Appl. Physiol. 80(1), 35–362.

    PubMed  Google Scholar 

  • FERNANDEZ, H. L., INESTROSA, N. C. & STILES, J. R. (1984) Subcellular localization of acetylcholinesterase molecular forms in endplate regions of adult mammalian skeletal muscle. Neurochem. R. 9, 121–1230.

    Google Scholar 

  • FERNANDEZ, H. L. & STILES, J. R. (1984) Denervation induced changes in subcellular pools of 16S acetylcholinesterase activity from adult mammalian skeletal muscle. Neurosci. L. 44, 18–192.

    Google Scholar 

  • FERNANDEZ-VALLE, C. & ROTUNDO, R. L. (1989) Regulation of acetylcholinesterase synthesis and assembly by muscle activity. J. Biol. Chem. –7.

  • FISCHBACH, G. D., FRANK, E., JESSELL, T. M., RUBIN, L. L. & SCHUETZE, S. M. (1979) Accumulation of acetylcholinesterase at newly formed nerve-muscle synapses. Pharm. Rev. 30, 41–428.

    Google Scholar 

  • FOURNIER, D., BERGE, J., CARDOSO DE ALMEIDA, M. & BORDIER, C. (1988) acetylcholinesterases from Musca Domestica and Drosophila melanogaster brain are linked to membranes by a glycophospholipid achor senestive to an endogenous phospholipase. J. Neurochem. 50, 115– 1163.

    PubMed  Google Scholar 

  • FUENTES, M. E., ROSENBERRY, T. L. & INESTROSA, N. C. (1988) A 13 kDa fragment is responsible for the hydrophobic aggregation of brain G4 acetylcholinesterase. Biochem. J. 256, 104–1050.

    PubMed  Google Scholar 

  • FUENTES, M. E. & TAYLOR, P. (1993) Control of acetylcholinesterase gene expression during myogenesis. Ref Type: Unpublished Work.

  • GAUTAM, M., NOAKES, P. G., MOSCOSO, L., RUPP, F., SCHELLER, R. H., MERLIE, J. P. & SANES, J. R. (1996) Defective neuromuscular synaptogensis in agrindeficient mutant mice. Cell 85, 52–535.

    PubMed  Google Scholar 

  • GAUTAM, M., NOAKES, P. G., MUDD, J., NICHOL, M., CHU, G. C., SANES, J. R. & MERLIE, J. P. (1995) Failure of postsynaptic specialization to develop at neuromuscular junctions of rapsyn-deficient mice. Nature 377(21), 23–236.

    PubMed  Google Scholar 

  • GEE, S. H., MONTANARO, F., LINDENBAUM, M. & CARBONETTO, S. (1994) Dystroglycan-?, a dystrophin-associated glycoprotein, is a functional agrin receptor. Cell 77, 67–686.

    PubMed  Google Scholar 

  • GETMAN, D. K., MUTERO, A., INOUE, K. & TAYLOR, P. (1995) Transcription factor repression and activation of the human acetylcholinesterase gene. (Unknown journal!) 2351–23519.

  • GIBNEY, G., MACPHEE-QUIGLEY, K., THOMPSON, B., VEDVICK, T., LOW, M. G., TAYLOR, S. S. & TAYLOR, P. B. (1988) Divergence in primary structure between the molecular forms of acetylcholinesterse. J. Biol. Chem. 263, 114–1145.

    PubMed  Google Scholar 

  • GOLDER, T. K., NIEBERG, P. S. & WILSON, B. W. (1977) Ultrastructural localization of acetylcholinesterase in cultured cells: II. Cycloheximide-treated emrbyo muscle. J. Hist. Cyto. 25, 37–383.

    Google Scholar 

  • GOLDER, T. K., NIEBERG, P. S. & WILSON, B. W. (1978) Ultrastructural localization of acetylcholinesterasae in cultured cells: III. DFP treated embryo muscle. J. Hist. Cyto. 26, 71–728.

    Google Scholar 

  • GRADY, R. M., MERLIE, J. P. & SANES, J. R. (1997a) Subtle neuromuscular defects in utrophin-deficient mice. J. Cell Biol. 136, 87–882.

    PubMed  Google Scholar 

  • GRADY, R. M., TENG, H., NICHOT, M. C., CUNNINGHAM, J. C., WILKINSON, R. S. & SANES, J. R. (1997b) Skeletal and cardiac myopathies in mice lacking utrophin and dystrophin: A model for duchenne muscular dystrophy. Cell 90, 72–738.

    PubMed  Google Scholar 

  • HAAS, R., MARSHALL, T. L. & ROSENBERRY, T. L. (1988) Drosophilia acetylcholinesterase: Demonstration of a glycoinositol phospholipid anchor and an endogenous proteolytic cleavage. Biochem. 27, 645–6457.

    Google Scholar 

  • HALL, Z. W. (1973) Multiple forms of acetylcholinesterase and their distribution in endplate and non-endplate regions of rat diaphragm muscle. J. Neurobiol. 4, 34– 361.

    PubMed  Google Scholar 

  • HALL, Z. W. & KELLY, R. B. (1979) Enzymatic detachment of endplate acetylcholinesterase frommuscle. Nature 232, 6–63.

    Google Scholar 

  • HALL, Z. W. & SANES, J. R. (1993) Synaptic structure and development: The neuromuscular junction. Cell/Neuron Review Supplement 72, 9–121.

    Google Scholar 

  • HENRY, M. D. & CAMPBELL, K. P. (1998) A role for dystroglycan in basement membrane assembly. Cell 95, 85–870.

    PubMed  Google Scholar 

  • HODGES-SAVOLA, C. A. & FERNANDEZ, H. L. (1995) A role for calcitonin gene-related peptide in the regulation of rat skeletal muscle G4 acetylcholinesterase. Neurosci. L. 190, 11–120.

    Google Scholar 

  • HUANG, C. F., TONG, J. & SCHMIDT, J. (1992) Protein kinase C couples membrane excitation at acetylcholine receptor gene inactivation in chick skeletal muscle. Neuron 9, 67–678.

    PubMed  Google Scholar 

  • INCARDONA, J. P. & ROSENBERRY, T. L. (1996a) Construction and characterization of secreted and chimeric transmembrane forms of drosophilia acetylcholinesterase: A large truncation of the C-terminal signal peptide does not eliminate glycoinositol phospholipid anchoring. Mol. Biol. of the Cell 7, 59–611.

    Google Scholar 

  • INCARDONA, J. P. & ROSENBERRY, T. L. (1996b) Replacement of the glycoinositol phospholipid anchor of drosophilia acetylcholinesterase with a transmembrane domain does not alter sorting in neurons and epithelia but results in behavioral defects. Mol. Biol. of the Cell 7, 61–630.

    Google Scholar 

  • INESTROSA, N. C. & PERELMAN, S. (1989) Distribution and anchoring of molecular forms of acetylcholinesterase. TIPS 10, 32–329.

    PubMed  Google Scholar 

  • INESTROSA, N. C., ROBERTS, W. L., MARSHALL, T. L. & ROSENBERRY, T. L. (1987) Acetylcholinesterase from bovine caudate nucleus is attached to membranes by a novel subunit distinct from those of acetylcholinesterase in other tissues. J. Biol. Chem. 262, 444–4444.

    PubMed  Google Scholar 

  • INESTROSA, N. C., SILBERSTIEN, L. & HALL, Z. W. (1982) Association of the synaptic forms of acetylcholinesterase with extracellar matrix in cultured mouse muscle cells. Cell 29, 7–79.

    PubMed  Google Scholar 

  • JACOBSON, C., COTE, P. D., ROSSI, S. G., ROTUNDO, R. L. & CARBONETTO, S. (2001) The dystroglycan complex is necessary for stabilization of acetylcholine receptor clusters at neuromuscular junctions and formation of the synaptic basement membrane. J. Cell Biol. 152, 43–450.

    PubMed  Google Scholar 

  • JASMIN, B. J., LEE, R. K. & ROTUNDO, R. L. (1993) Compartmentalization of acetylcholinesterase mRNA and enzyme at the vertebrate neuromuscular junction. Neuron 11, 46–477.

    PubMed  Google Scholar 

  • JEDRZEJCZYK, J., SILMAN, I., LYLES, J. M. & BARNARD, E. A. (1981) Molecular forms of the cholinesterase inside and outside muscle endplates. Bioscience Reports 1, 4–51.

    PubMed  Google Scholar 

  • JOHNSON, C. D. & RUSSELL, R. L. (1975) A rapid, simple radiometric assay for cholinesterase, suitable for multiple determinations. Analytical Biochem. 64, 22–238.

    Google Scholar 

  • KARNOVSKY, M. J. & ROOTS, L. (1964) A “direct coloring” thiocholine method for cholinesterase. Cytochemistry 12, 219. (Ref Type: Generic).

    Google Scholar 

  • KASPRZAK, H. & SALPETER, M. M. (1985) Recovery of acetylcholinesterase at intact neuromuscular junctions after in vivo inactivation with diisopropylfluorophoosphate. J. Neurosc. 5, 95–955.

    Google Scholar 

  • KIMBELL, K. M., OHNO, K., ENGEL, A. G. & ROTUNDO, R. L. (2004) C-terminal and heparin binding domains of ColQ are both essential for anchoring acetylcholinesterase at the synapse. J. Biol. Chem. (in press).

  • KOELLE, G. B. & FRIEDENWALD, J. S. (1949) A histochemical method for localizing cholinesterase activity. Proc. Soc. Exp. Biol. Med. N.Y. 70, 617.

    Google Scholar 

  • KOELLE, W. A. & KOELLE, G. B. (1959) The localization of external or functional acetylcholinesterase at the synapses of autonomic gangia. J. Pharm. Exp. 126, –8.

    Google Scholar 

  • KOENIG, J. (1978) Formation de jonctions neuromusculaires dans des cultures cellullaires embryonnaires de Rat. C. R. Acad. Paris. 286, 145–1453.

    Google Scholar 

  • KOENIG, J. (1979) Formation and maturation of nervemuscle contacts in cultured rat embryo cells. Bio. Cell. 35, 14–152.

    Google Scholar 

  • KOENIG, J., OREN, M. & MELONE, M. A. B. (1982) Establishment of neruomuscular contacts in cultures of rat embryonic cells: Effects of tetrodotoxin on maturation of muscle fibers and on formation and maintenance of acetylcholinesterase and acetylcholine receptor clusters. Dev. Neurosci. 5, 31–325.

    PubMed  Google Scholar 

  • KREJCI, E., COUSSEN, F., DUVAL, N., CHATEL, J. M., LEGAY, C., PUYPE, M., VANDEKERCKHOVE, J., CARTAUD, J., BON, S. & MASSOULIÉ, J. (1991) Primary structure of a collagenic tail peptide of torpedo acetylcholinesterase: Co-expression with catalytic subunit induces the production of collagen-tailed forms in tranfected cells. The EMBO Journal 10, 128–1293.

    PubMed  Google Scholar 

  • KREJCI, E., LEGAY, C., THOMINE, S., SKETELJ, J. & MASSOULIÉ, J.(1999) Differences in expression of acetylcholinesterase and collagen Q control the distribution and oligomerization of the collagen-tailed forms in fast and slow muscles. J. Neurosci. 19, 1067–10679.

    PubMed  Google Scholar 

  • KREJCI, E., THOMINE, S., BOSCHETTI, N., LEGAY, C., SKETELJ, J. & MASSOULIÉ, J. (1997) The mammalian gene of acetylcholinesterase-associated collagen. The Journal of Bio. Chem. 272(36), 2284–22847.

    Google Scholar 

  • KRONMAN, C., CHITLARU, T., ELHANANY, E., VELAN, B. & SHAFFERMAN, A. (2000) Hierarchy of post-translational modifications involved in the circulatory longevity of glycoproteins. Demonstration of concerted contributions of glycan sialylation and subunit assembly to the pharmacokinetic behavior of bovine acetylcholinesterase. J. Biol. Chem. 275, 2948–29502.

    PubMed  Google Scholar 

  • KRONMAN, C., VELAN, B., MARCUS, D., ORDENTLICH, A., REUVENY, S. & SHAFFERMAN, A. (1995) Involvement of oligomerization, Nglycosylation and sialylation in the clearance of cholinesterases from the circulation. Biochem. J. 311(Pt 3), 95–967.

    PubMed  Google Scholar 

  • LEE, S. & TAYLOR, P. B. (1982) Structural characterization of the asymmetric (17 + 13) S Species of acetylcholinesterase from Torpedo: Component peptides obtained by selective proteolysis and disulfide bond reduction. J. Biol. Chem. 257, 1229–12301.

    PubMed  Google Scholar 

  • LEE, S., CAMP, S. J. & TAYLOR, P. B. (1982a) Characterization of a hydrophobic, dimeric form of acetylcholinesterase from Torpedo. J. Biol. Chem. 257, 1230–12309.

    PubMed  Google Scholar 

  • LEE, S. L., HEINEMANN, S. & TAYLOR, P. B. (1982b) Structural characterization of the asymmetric (17 + 13) forms of acetylcholinesterase from Torpedo: Analysis of subunit composition. J. Biol. Chem. 257, 1228–12291.

    Google Scholar 

  • LEGAY, C. (2000) Why so many forms of acetylcholinesterase? Microscopy Research and Technique 49, 5–72.

    PubMed  Google Scholar 

  • LEGAY, C., BON, S. & MASSOULIÉ, J. (1993a) Expression of a cDNA-encoding glycolipid-anchored form of rat acetylcholinesterase. FEBS Letters 315(2), 16–166.

    PubMed  Google Scholar 

  • LEGAY, C., BON, S., VERNIER, P., COUSSEN, F. & MASSOULIÉ, J. (1993b) Cloning and expression of a rat acetylcholinesterase subunit: Generation of multiple molecular forms and complementarity with a Torpedo collagenic subunit. Journal of Neurochem. 60, 33–345.

    Google Scholar 

  • LEGAY, C., HUCHET, M., MASSOULIÉ, J. & CHANGEUX, J.-P. (1995) Developmental regulation of acetylcholinesterase transcripts in the mouse diaphragm: Alternative splicing and focalization. European Journal of Neuroscience 7, 180–1809.

    PubMed  Google Scholar 

  • LEGAY, C., MANKAL, F. A., MASSOULIÉ, J. & JASMIN, B. J. (1999) Stability and secretion of acetylcholinesterase forms in skeletal muscle cells. J. Neurosci. 19, 825– 8259.

    PubMed  Google Scholar 

  • LI, Y., CAMP, S., RACHINSKY, T. L., BONGIORNO, C. & TAYLOR, P. (1993) Promoter elements and transcriptional control of the mouse acetylcholinesterase gene. J. Biol. Chem. 268, 356–3572.

    PubMed  Google Scholar 

  • LI, Y., CAMP, S., RACHINSKY, T. L., GETMAN, D. & TAYLOR, P. (1991) Gene structure ofmammalianacetylcholinesterase. Alternative exons dictate tissue-specific expression. J. Biol. Chem. 266, 2308–23090.

    PubMed  Google Scholar 

  • LI, Y., CAMP, S. & TAYLOR, P. (1993b) Tissue-specific expression and alternate mRNA processing of the mammilian acetylcholinesterase gene. The Journal of Bio. Chem. 268, 579–5797.

    Google Scholar 

  • LI, Z. & BON, C. (1983) Presence of a membrane-bound acetylcholinesterase form in a preparation of nerve endings from Torpedo Marmorata electric organ. J. Neurochem. 40, 33–349.

    PubMed  Google Scholar 

  • LIN, W., BURGESS, R. W., DOMINGUEZ, B., PFAFF, S. L., SANES, J. R. & LEE, K. F. (2001) Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse. Nature 410, 105–1064.

    PubMed  Google Scholar 

  • LINKHART, T. A. & WILSON, B. W. (1975) Appearance of acetylcholinesterase and creatine kinase in plasma of normal chickens after denervation. J. Neur. Sci. 26, 19–201.

    Google Scholar 

  • LOCKRIDGE, O. (1988) Structure of human serum cholinesterase. BioEssays 9(4), 12–128.

    PubMed  Google Scholar 

  • LOCKRIDGE, O., BARTELS, C. F., VAUGHAN, T. A., WONG, C. K., NORTON, S. E. & JOHNSON, L. L. (1987) Complete amino acid sequence of human serum cholinesterase. J. Biol. Chem. 262, 54–557.

    PubMed  Google Scholar 

  • LOCKRIDGE, O., ECKERSON, H. W. & LA DU, B. N. (1979) Interchain disulfide bonds and subunit organization in human serum cholinesterase. J. Biol. Chem. 254, 832–8330.

    PubMed  Google Scholar 

  • LOCKRIDGE, O. & LA DU, B. N. (1982) Loss of the interchain disulfide peptide and dissociation of the tetramer following limited proteolysis of native human serum cholinesterase. J. Biol. Chem. 257, 1201–12018.

    PubMed  Google Scholar 

  • LOMO, T., MASSOULIÉ, J. & VIGNY, M. (1985) Stimulation of denervated rat soleus muscle with fast and slow activity patterns induces different expression of acetylcholinesterase molecular forms. J. Neurosci. 5, 118–1187.

    PubMed  Google Scholar 

  • LOMO, T. & SLATER, C. R. (1980) Control of junctional acetylcholinesterase by neural and muscular influences in the rat. J. Physiol. 303, 19–202.

    PubMed  Google Scholar 

  • LUIZ DA COSTA JR, V., LAPA, A. J. & GODINHO, R. O. (2001) Short-and long-term influences of calcitonin generelated peptide on the synthesis of acetylcholinesterase in mammalian myotubes. British Journal of Pharmacology 133, 22–236.

    PubMed  Google Scholar 

  • LWEBUGA-MUKASA, J. S., LAPPI, S. & TAYLOR, P. (1976) Molecular forms of acetylcholinesterase from Torpedo californica: Their relationship to synaptic membranes. Biochemistry 15, 142–1434.

    PubMed  Google Scholar 

  • MARNAY, A. & NACHMANSOHN, D. (1937) Sur la repartition de la cholinesterase dans le muscle couturier de la grenouille. Comp. Rend. Soc. Biol. 125, 4–47.

    Google Scholar 

  • MASSOULIÉ, J. & BON, S. (1976) Affinity chromatography of acetylcholinesterase: The importance of hydrophobic interactions. Eur. J. Biochem. 68, 53–539.

    PubMed  Google Scholar 

  • MASSOULIÉ, J., PESSEMENTI, L., BON, S., KREJCI, E. & VALLETTE, F. M. (1993) Molecular and cellular biology of cholinesterases. Progress in Neurobiology 41, 3–91.

    PubMed  Google Scholar 

  • MASSOULIÉ, J. & RIEGER, F. (1969) L'Acetylcholinesterase des organes electriques de Poissons (Torpille et Gymnote): Complexes membranaires. Eur. J. Biochem. 11, 44–455.

    PubMed  Google Scholar 

  • MASSOULIÉ, J., SUSSMAN, J. L., DOCTOR, B. P., SOREQ, H., VELAN, B., CYGLER, M., ROTUNDO, R. L., SCHAFFERMAN, A., SILMAN, I. & TAYLOR, P. (1992) Recommendations for nomenclature in cholinesterases. In Multidisciplinary Approaches to Cholinesterase Functions (edited by SCHAFFERMAN, A. & VELAN, B.) pp. 28–288. New York: Plenum Press.

    Google Scholar 

  • MAULET, Y., CAMP, S., GIBNEY, G., RACHINSKY, T. L., EKSTROM, T. J. & TAYLOR, P. (1990) Single gene encodes glycophospholipid-anchored and asymmetric acetylcholinesterase forms: Alternate coding exons contain inverted repeat sequences. Neuron 4, 28–301.

    PubMed  Google Scholar 

  • MAYS, C. & ROSENBERRY, T. L. (1981) Characterization of pepsin-resistant collagen-like tail subunit fragments of 18S and 14S acetylcholinesterase from Electrophorus electricus. Biochemistry 20, 281–2817.

    PubMed  Google Scholar 

  • MCISAAC, R. J. & KOELLE, G. B. (1959) Comparison of the effects of inhibition of external internal and total acetylycholinesterase upon ganglionic transmission. J. Pharm. Exp. 126, –20.

    Google Scholar 

  • MCMAHAN, U. J. (1990) The agrin hypothesis. Cold Spring Harb. Symp. Quant. Biol. 55, 40–418.

    PubMed  Google Scholar 

  • MCMAHAN, U. J., SANES, J. R. & MARSHALL, L. M. (1978) Cholinesterase is associated with the basal lamina at the neuromuscular junction. Nature 271, 17–174.

    PubMed  Google Scholar 

  • MEFLAH, K., BERNARD, S. & MASSOULIÉ, J. (1984) Interactions with lectins indicate differences in the carbohydrate composition of the membrane-bound enzymes acetylcholinesterase and 5?-nucleotidase in different cell types. Biochimie 66, 5–69.

    PubMed  Google Scholar 

  • MENDELZON, D., CHANGEUX, J.-P. & NGHIEM, H.-O. (1994) Phosphorylation of myogenin in chick myotubes: Regulation by electrical activity and by protein kinase C. implication for acetylcholine receptor gene expression. Biochemistry 33, 256–2575.

    PubMed  Google Scholar 

  • MERLIE, J. P. & SANES, J. R. (1985) Concentration of acetylcholine receptor mRNA in synaptic regions of adult muscle fibres. Nature 317, 6–68.

    PubMed  Google Scholar 

  • MICHEL, R. N., VU, C. Q., TETZLAFF, W. & JASMIN, B. J. (1994) Neural regulation of acetylcholinesterase mRNAs at mammalian neuromuscular synapses. J. Cell Biol. 127, 106–1069.

    PubMed  Google Scholar 

  • MOODY-CORBETT, F. & COHEN, M. W. (1981) Localization of cholinesterase at sites of high acetylcholine receptor density on embryonic amphibian muscle cells cultured without nerve. Neuroscienc.

  • MOODY-CORBETT, F. & COHEN, M. W. (1982) Influence of nerve on the formation and survival of acetylcholine receptor and cholinesterase patches on embryonic Xenopus muscle cells in culture. J. Neurosc. 2, 63–646.

    Google Scholar 

  • MOODY-CORBETT, F., WELDON, P. R. & COHEN, M. W. (1982) Cholinesterase localization at sites of nerve contact on embryonic amphibian muscle cells in culture. J. Neurocyt. 11, 38–394.

    Google Scholar 

  • MUTERO, A., CAMP, S. & TAYLOR, P. (1995) Promoter elements of the mouse acetylcholinesterase gene. Transcriptional regulation during muscle differentiation. J. Biol. Chem. 270, 186–1872.

    PubMed  Google Scholar 

  • NEVILLE, C. M., SCHMIDT, M. & SCHMIDT, J. (1992) Response of myogeneic determination factors to cessation and resumption of electrical-activity in skeletalmuscle— a possible role for muogenin in denervation supersensitivity. Cell. Mol. N. 12(6), 51–527.

    Google Scholar 

  • NOAKES, P. G., GAUTAM, M., MUDD, J., SANES, J. R. & MERLIE, J. P. (1995) Aberrant differentiation of neuromuscular junctions in mice lacking s-laminin/laminin ?2. Nature 374, 25–262.

    PubMed  Google Scholar 

  • OHNO, K., BRENGMAN, J., TSUJINO, A. & ENGEL, A. G. (1998) Human endplate acetylcholinesterase deficiency caused by mutations in the collagen-like tail subunit (ColQ) of the asymmetric enzyme. Proc. Natl. Acad. Sci. USA 95, 965–9659.

    PubMed  Google Scholar 

  • OHNO, K., ENGEL, A. G., BRENGMAN, J., SHEN, X., HEIDENREICH, F., VINCENT, A., MILONE, M., TAN, E., DEMIRCI, M., WALSH, P., NAKANO, S. & AKIGUCHI, I. (2000) The spectrum of mutations causing end-plate acetylcholinesterase deficiency. Ann. Neurol. 47, 16–170.

    PubMed  Google Scholar 

  • ORDAHL, C. P. & LE DOUARIN, N. M. (1992) Two myogenic lineages within the developing somite. Development 114, 33–353.

    PubMed  Google Scholar 

  • PALADE, G. (1975) Intracellular aspects of the process of protein synthesis. Science 189, 34–358.

    PubMed  Google Scholar 

  • PARTON, R. G., SIMONS, K. & DOTTI, C. G. (1992) Axonal and dendritic endocytic pathways in cultured neurons. J. Cell Biol. 119, 12–137.

    PubMed  Google Scholar 

  • PENG, H. B., ALI, A. A., DAGGETT, D. F., RAUVALA, H., HASSELL, J. R. & SMALHEISER, N. R. (1998) The relationship between perlecan and dystroglycan and its implication in the formation of the neuromuscular junction. Cell Adhes. Commun. 5, 47–489.

    PubMed  Google Scholar 

  • PENG, H. B., GAO, K.-X., XIE, M.-Z. & ZHAO, D.-Y. (1988) Development of acetylcholinesterase induced by basic polypeptide-coated latex beads in cultured xenopus muscle cells. Develop. Biol. 127, 45–455.

    PubMed  Google Scholar 

  • PENG, H. B., XIE, H., ROSSI, S. G. & ROTUNDO, R. L. (1999) Acetylcholinesterase clustering at the neuromuscular junction involves perlecan and dystroglycan. J. Cell Biol. 145, 91–921.

    PubMed  Google Scholar 

  • PERRIER, A. L., MASSOULIÉ, J. & KREJCI, E. (2002) PRiMA: The membrane anchor of acetylcholinesterase in the brain. Neuron 33, 27–285.

    PubMed  Google Scholar 

  • PHILLIPS, W. D., NOAKES, P. G., ROBERDS, S. L., CAMPBELL, K. P. & MERLIE, J. P. (1993) Clustering and immobilization of acetylcholine receptors by the 43-kD protein: A possible role for dystropin-related protein. The Journal of Cell Biology 123(3), 72–740.

    PubMed  Google Scholar 

  • PREGELJ, P. & SKETELJ, J. (2000) Effect of mechanical load on acetylcholinesterase mRNA levels in the slow soleus muscle of the rat. Pflugers Arch. 440, R11–R114.

    PubMed  Google Scholar 

  • PREGELJ, P. & SKETELJ, J. (2002) Role of load bearing in acetylcholinesterase regulation in rat skeletal muscles. J. Neurosci. Res. 67, 11–121.

    PubMed  Google Scholar 

  • PRIVES, J., SILMAN, I. & AMSTERDAM, A. (1976) Appearance and disappearance of acetylcholine receptor during differentiation of chick skeletal muscle in vitro. Cell. 7, 54–550.

    PubMed  Google Scholar 

  • PRIVES, J. M. & PATERSON, B. M. (1974) Differentiation of cell membranes in cultures of embryonic chick breast muscle. Proc. Natl. Acad. Sci. USA 71, 320–3211.

    PubMed  Google Scholar 

  • RANDALL, W. R. (1994) Cellular expression of a cloned, hydrophilic, murine acetylcholinesterase: Evidence of palmitoylated membrane-bound forms. J. Biol. Chem. 269, 1236–12374.

    PubMed  Google Scholar 

  • RANDALL, W. R., RIMER, M. & GOUGH, N. R. (1994) Cloning and analysis of chicken acetylcholinesterase transcripts from muscle and brain. Biochimica et Biophysica Acta 121, 45–456.

    Google Scholar 

  • RIBARIC, S., ROZMAN, J. & SKETELJ, J. (2000) Modification of skeletal muscle AChE expression by a novel method of stimulus application to the peripheral nerve. Pflugers Arch. 439, R21–R219.

    PubMed  Google Scholar 

  • RIEGER, F., KOENIG, J. & VIGNY, M. (1980) Spontaneous contractile activity and the presence of the 16 S form of acetylcholinesterase in rat muscle cells in culture: Reversible suppressive action of tetrodotoxin. Dev. Biol. 76, 35–365.

    PubMed  Google Scholar 

  • ROSENBERRY, T. L. (1975) Acetylcholinesterase. In Advances in Enzymology and Related Areas of Molecular Biology (edited byMEISTER, A.)Vol. 43, pp. 10–218. JohnWiley & Sons Inc. Publishers.

  • ROSENBERRY, T. L., CHANG, H. W. & CHEN, Y. T. (1972) Purification of acetylcholinesterase by affinity chromatography and determination of active site stoichiometry. J. Biol. Chem. 217, 155–1565.

    Google Scholar 

  • ROSENBERRY, T. L. & RICHARDSON, J. M. (1977) Structure of 18S and 14S acetylcholinesterase. Identification of collagen-like subunits that are linked by disulfide bonds to catalytic subunits. Biochem. 16, 355–3558.

    Google Scholar 

  • ROSENBERRY, T. L. & SCOGGIN, D. M. (1984) Structure of human erythrocyte acetylcholinesterase: Characterization of intersubunit disulfide bonding and detergent interaction. J. Biol. Chem. 259, 564–5652.

    PubMed  Google Scholar 

  • ROSSI, S. G., KATZ, S. & ROTUNDO, R. L. (1997) Control of acetylcholinesterase gene expression in tissuecultured skeletal muscle: Opposite regulation by protein kinases A and C. 10th International Symposium on Cholinergic Mechanisms 48–487.

  • ROSSI, S. G. & ROTUNDO, R. L. (1996) Transient interactions between collagen-tailed acetylcholinesterase and sulfated proteoglycans prior to immobilization on the extracellular matrix. J. Biol. Chem. 271(4), 197–1987.

    PubMed  Google Scholar 

  • ROSSI, S. G. & ROTUNDO, R. L. (1992) Cell surface acetylcholinesterase molecules on multinucleated myotubes are clustered over the nucleus of origin. J. Cell Biol. 119, 165–1667.

    PubMed  Google Scholar 

  • ROSSI, S. G. & ROTUNDO, R. L. (1993) Localization of “non-extractable” acetylcholinesterase to the vertebrate neuromuscular junction. J. Biol. Chem. 268, 1915– 19159.

    PubMed  Google Scholar 

  • ROSSI, S. G., VAZQUEZ, A. E. & ROTUNDO, R. L. (2000) Local control of acetylcholinesterase gene expression in multinucleated skeletal muscle fibers: Individual nuclei respond to signals fromthe overlying plasma membrane. J. Neurosci. 20, 91–928.

    PubMed  Google Scholar 

  • ROTUNDO R. L. & FAMBROUGH, D. M. (1994) Function and molecular structure of acetylcholinesterase. In Myology (edited by ENGEL, A. G. & FRANZINIARMSTRONG, C.). New York: McGraw-Hill.

    Google Scholar 

  • ROTUNDO, R. L. (1984a) Asymmetric acetylcholinesterase is assembled in the golgi apparatus. Proc. Natl. Acad. Sci. USA 81, 47–483.

    PubMed  Google Scholar 

  • ROTUNDO, R. L. (1984b) Purification and properties of the membrane-bound form of acetylcholinesterase form chicken brain. J. Biol. Chem. 259(21), 1318–13194.

    PubMed  Google Scholar 

  • ROTUNDO, R. L. (1984c) Synthesis, assembly, and processing of AChE in tisse cultured muscle. In cholinesterase (edited by BRZIN, M., BARNARD, E. A. & SKET, D.) pp. 20–217. Berlin-New York: Walter de Gruyter Co.

    Google Scholar 

  • ROTUNDO, R. L. (1988) Biogenesis of acetylcholinesterase molecular forms in muscle: Evidence for rapidly turnning over, catalytically inactive precursor pool. J. Biol. Chem. 263(36), 1939–19406.

    PubMed  Google Scholar 

  • ROTUNDO, R. L. & FAMBROUGH, D. M. (1979) Molecular forms of chicken embryo acetycholinesterase in vitro and in vivo. J. Biol. Chem. 254(11), 479–4799.

    PubMed  Google Scholar 

  • ROTUNDO, R. L. & FAMBROUGH, D. M. (1980a) Secretion of acetylcholinesterase: Relation to acetylcholine receptor metabolism. Cell 22, 59–602.

    PubMed  Google Scholar 

  • ROTUNDO, R. L. & FAMBROUGH, D. M. (1980b) Synthesis, transport and fate of acetylcholinesterase in cultured chick embryo muscle cells. Cell 22, 58–594.

    PubMed  Google Scholar 

  • ROTUNDO, R. L., GOMEZ, A. M., FERNANDEZVALLE, C. & RANDALL, W. R. (1988) Allelic variants of acetylcholinesterase: Genetic evidence that all acetylcholinesterase forms in avian nerves and muscles are encoded by a single gene. Proc. Natl. Acad. Sci. USA 85, 780–7809.

    PubMed  Google Scholar 

  • ROTUNDO, R. L., ROSSI, S. G. & ANGLISTER, L. (1997) Transplantation of quail collagen-tailed acetylcholinesterase molecules onto the frog neuromuscular synapse. J. Cell Biol. 136, 36–374.

    PubMed  Google Scholar 

  • ROTUNDO, R. L., THOMAS, K., PORTER-JORDAN, K., BENSON, R. J. J., FERNANDEZ-VALLE, C. & FINE, R. E. (1989) Intracellular transport, sorting, and turnover of acetylcholinesterase: Evidence for endoglycosidase Hsensitive form in golgi apparatus, sarcoplasmic reticulum, and clathrin-coated vesicles and its rapid degradation by a non-Lysosomal mechanism. J. Biol. Chem. 264(6), 314–3152.

    PubMed  Google Scholar 

  • RUBIN, L. L. (1985) Increases in muscle Ca(2+) Mediate changes in acetylcholinesterase and acetylchlolie receptors caused by muscle contraction. Proc. Natl. Acad. Sci. USA 82, 712–7125.

    PubMed  Google Scholar 

  • RUBIN, L. L., SCHUETZE, S. M. & FISCHBACH, G. D. (1979) Accumulation of acetylcholinesterase at newly formed nerve-muscle synapses. Develop. Biol. 69, 4– 58.

    PubMed  Google Scholar 

  • SALPETER, M. M. (1967) Electron microscope radioautography as a quantitative tool in enzyme cytochemistry. The Journal of Cell Biology 32, 37–389.

    PubMed  Google Scholar 

  • SALPETER, M. M., ROGERS, A. W., KASPRZAK, H. & MCHENRY, F. A. (1978) acetylcholinesterase in the fast extraocular muscle of the mouse by light and electron microscope autoradiography. J. Cell Biol. 78, 27–285.

    PubMed  Google Scholar 

  • SANES,J.R.& CHENEY,J.M. (1982) Lectin binding reveals a synapse-specific carbohydrate in skeletal muscle. Nature 300, 64–647

    PubMed  Google Scholar 

  • SANES, J. R. & LICHTMAN, J. W. (1999) Development of the vertebrate neuromuscular junction. Annu. Rev. Neurosci. 22, 38–442.

    PubMed  Google Scholar 

  • SANES, J. R. & LICHTMAN, J. W. (2001) Induction, assembly, maturation and maintenance of a postsynaptic apparatus. Nat. Rev. Neurosci. 2, 79–805.

    PubMed  Google Scholar 

  • SAWYER, H. R., GOLDER, T. K., NIEBERG, P. S. & WILSON, B. W. (1976) Ultrastructural localization of acetylcholinesterase in cultured cells: I. embryo muscle. J. Hist. Cyto. 24, 96–978.

    Google Scholar 

  • SAXENA, A., ASHANI, Y., RAVEH, L., STEVENSON, D., PATEL, T. & DOCTOR, B. P. (1998) Role of oligosaccharides in the pharmacokinetics of tissue-derived amd genetically engineered cholinesterase. Molecular Pharmacology 53, 11–122.

    PubMed  Google Scholar 

  • SAXENA, A., RAVEH, L., ASHANI, Y. & DOCTOR, B. P. (1997) Structure of glycan moieties responsible for the extended circulatory life time of fetal bovine serum acetylcholinesterase and equine serum butyrylcholinesterase. Biochem. 36, 748–7489.

    Google Scholar 

  • SCHAEFFER, L., DE KERCHOVE D'EXAERDE, A. & CHANGEUX, J.-P. (2001) Targeting transcription to the neuromuscular synapse. Neuron 31, 1–22.

    PubMed  Google Scholar 

  • SCHUMACHER, M., CAMP, S. J., MAULET, Y., NEWTON, M., MACPHEE-QUIGLEY, K., TAYLOR, S. S., FRIEDMANN, T. & TAYLOR, P. B. (1986) Primary structure of Torpedo californica acetylcholinesterase deduced from its cDNA sequence. Nature 319, 40–409.

    PubMed  Google Scholar 

  • SCHUMACHER, M., MAULET, Y., CAMP, S. J. & TAYLOR, P. B. (1988) Multiple Messenger RNA species give rise to the sructural diversity in acetylcholinesterase. J. Biol. Chem. 263, 1897–18987.

    PubMed  Google Scholar 

  • SCOTT, L. J. C., BACOU, F. & SANES, J. R. (1988) A synapse-specific carbohydrate at the neuromuscular junction: Association with both acetylcholinesterase and a glycolipid. J. Neurosc. 8, 93–944.

    Google Scholar 

  • SCOTT, L. J. C., BALSAMO, J., SANES, J. R. & LILIEN, J. (1990) Synaptic locatization and neural regulation of an N-acetylgalactosaminyl transferase in skeletal muscle. J. of Neuroscience 10, 34–350.

    Google Scholar 

  • SIKORAV, J.-L., DUVAL, N., ANSELMET, A., BON, S., KREJCI, E., LEGAY, C., OSTERLUND, M., REIMUND, B. & MASSOULIÉ, J. (1988) Complex alternative splicing of acetylcholinesterase transcripts in Torpedo electric organ; Primary structure of the precursor of the glycolipid-anchored dimeric form. EMBO. J. 7, 298–2993.

    PubMed  Google Scholar 

  • SIKORAV, J. L., KREJCI, E. & MASSOULIÉ, J. (1987) cDNA sequences of Torpedo marmorata acetylcholinesterase: Primary structure of the precursor of a catalytic subunit; existence of multiple 5'-untranslated regions. EMBO J. 6, 186–1873.

    PubMed  Google Scholar 

  • SIMON, S., KREJCI, E. & MASSOULIÉ, J. (1998) Afour-toone association between peptide motifs: Four C-terminal domains from cholinesterase assemble with one prolinerich attachment domain (PRAD) in the secretory pathway. EMBO J. 17, 617–6187.

    PubMed  Google Scholar 

  • SKAU, K. A. & BRIMIJOIN, S. (1980) Multiple molecular forms of acetylcholinesterase in rat vagus nerve, smooth muscle, and heart. J. Neurochem. 35, 115–1154.

    PubMed  Google Scholar 

  • SKETELJ, J. & BRZIN, M. (1979) Attachment of acetylcholinesterase to structures of the motor endplate. Histochem. 61, 23–248.

    Google Scholar 

  • SKETELJ, J., CRNE-FINDERLE, N., STRUKELJ, B., TRONTELJ, J. V. & PETTE, D. (1998) Acetylcholinesterase mRNA level and synaptic activity in rat muscles depend on nerve-induced pattern of muscle activation. J. Neurosci. 18, 194–1952.

    PubMed  Google Scholar 

  • SKETELJ, J., LEISNER, E., GOHLSCH, B., SKORJANC, D. & PETTE, D. (1997) Specific impulse patterns regulate acetylcholinesterase activity in skeletal muscles of rats and rabbits. J. Neurosci. Res. 47, 4–57.

    PubMed  Google Scholar 

  • SOREQ, H., BEN-AZIZ, R., PRODY, C. A., SEIDMAN, S., GNATT, A., NEVILLE, L., LIEMAN-HURWITZ, J., LEV-LEHMAN, E., GINZBERG, D., LAPIDOTLIFSON, Y. & ZAKUT, H. (1990) Molecular cloning and construction of the coding region for human acytlcholinesterase reveals aG+C-rich attenuation structure. Proc. Natl. Acad. Sci. 87, 968–9692.

    PubMed  Google Scholar 

  • SUSSMAN, J. L., HAREL, M., FROLOW, F., OEFNER, C., GOLDMAN, A., TOKER, L. & SILMAN, I. (1991) Atomic structure of acetylcholinesterase from Torpedo californica: A prototypic acetylcholine-binding protein. Science 253, 87–879.

    PubMed  Google Scholar 

  • TALTS, J. F., ANDAC, Z., GOHRING, W., BRANCACCIO, A. & TIMPL, R. (1999) Binding of the G domains of laminin alpha1 and alpha2 chains and perlecan to heparin, sulfatides, alpha-dystroglycan and several extracellular matrix proteins. EMBO J. 18, 86–870.

    PubMed  Google Scholar 

  • TAYLOR, P. (1991) The cholinesterases. The Journal of Bio. Chem. 266, 402–4028.

    Google Scholar 

  • TORRES, J. C. & INESTROSA, N. C. (1985) Interaction of heparin with multimolecular aggregates of acetylcholinesterase. Cell. Mol. N. 5, 30–309.

    Google Scholar 

  • TSIM, K. W. K., RANDALL, W. R. & BARNARD, E. A. (1988a) An asymmetric from of muscle acetylcholinesterase contains three subunit types and two enzymic activities in one molecule. Proc. Natl. Acad. Sci.USA 85, 126–1266.

    PubMed  Google Scholar 

  • TSIM, K. W. K., RANDALL, W. R. & BARNARD, E. A. (1988b) Monoclonal antibodies apecific for the different subunits of asymmetric acetylcholinesterase from chick muscle. J. Neurochem. 51, 9–104.

    PubMed  Google Scholar 

  • VALLETTE, F. M., DE LA, P. S., KOENIG, J., MASSOULIÉ, J. & VIGNY, M. (1990) Acetylcholinesterase in cocultures of rat myotubes and spinal cord neurons: Effects of collagenase and cishydroxyproline on molecular forms, intra-and extracellular distribution, and formation of patches at neuromuscular contacts. J. Neurochem. 54, 91–923.

    PubMed  Google Scholar 

  • VELAN, B., KRONMAN, C., ORDENTLICH, A., FLASHNER, Y., LEITNER, M., COHEN, S. & SHAFFERMAN, A. (1993) N-glycosylation of human acetylcholinesterase: Effects on activity, stability and biosynthesis. Biochem. J. 296(Pt 3), 64–656.

    PubMed  Google Scholar 

  • VIGNY, M., DI GIAMBERARDINO, L., COURAUD, J. Y., RIEGER, F. & KOENIG, J. (1976a) Molecular forms of chicken acetylcholinesterase: Effect of denervation. FEBS Lett. 69, 27–280.

    PubMed  Google Scholar 

  • VIGNY, M., KOENIG, J. & RIEGER, F. (1976b) The motor end-plate specific form of acetylcholinesterase: Appearance during embryogenesis and re-innervation of rat muscle. J. Neurochem. 27, 134–1353.

    PubMed  Google Scholar 

  • WALKER, C. R. & WILSON, B. W. (1976) Regulation of acetylcholinesterase in chich muscle culture after treatment with diisiopropylphosphorofluoridate: Ribonucleic acid and protein synthesis. Neurosci. 1, 50– 513.

    Google Scholar 

  • WALLACE, B. G. (1989) Agrin-Induced specialization contain cytoplasmic, membrane, and extracellualar matrixassociated components of the postsynaptic apparatus. J. Neurosci. 9(4), 129–1302.

    PubMed  Google Scholar 

  • WALLACE, B. G., NITKIN, R. M., REIST, N. E., FALLON, J. R., MOAYERI, N. N. & MCMAHAN, U. J. (1985) Aggregates of acetylcholinesterase induced by acetylcholine receptor-aggregating factor. Nature 315, 57– 577.

    PubMed  Google Scholar 

  • WEINBERG, C. B. & HALL, Z. W. (1979) Junctional form of acetylcholinesterase restored at nerve-free endplates. Develop. Biol. 68, 63–635.

    PubMed  Google Scholar 

  • WELDON, P. R., MOODY-CORBETT, F. & COHEN, M. W. (1981) Ultrastucture of sites of cholinesterase activity on amphibian embyronic muscle cells cultured without nerve. Develop. Biol. 84, 34–350.

    Google Scholar 

  • WILSON, B. W. & WALKER, C. R. (1974a) Mobilization and release of newly synthesized acetylcholinesterase in cultured muscle. In Exploratory Concepts in Muscular Dystrophy II. (edited by MILHORAT, A. T.) pp. 13–153. New York: Excerpta Medica/American Elevier.

    Google Scholar 

  • WILSON, B. W. & WALKER, C. R. (1974b) Regulation of newly synthesized acetylcholinesterase in muscle culture treated with diisopropylfluorophosphate. Proc. Natl. Acad. Sci. USA 71, 319–9198.

    PubMed  Google Scholar 

  • YOUNKIN, S. G., ROSENSTEIN, C., COLLINS, P. L. & ROSENBERRY, T. L. (1982) Cellular localization of the molecular forms of acetylcholinesterase in rat diaphragm. J. Biol. Chem. 257, 1363–13637.

    PubMed  Google Scholar 

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  1. Department of Cell Biology and Anatomy and Neuroscience Program, University of Miami School of Medicine, Miami, Florida, 33136, USA

    Richard L. Rotundo

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Rotundo, R.L. Expression and localization of acetylcholinesterase at the neuromuscular junction. J Neurocytol 32, 743–766 (2003). https://doi.org/10.1023/B:NEUR.0000020621.58197.d4

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Keywords

  • Acetylcholinesterase
  • Basal Lamina
  • Neuromuscular Junction
  • Neuromuscular Transmission
  • Hydrophobic Character