Abstract
Clathrin, which constitutes coated vesicles, plays important roles in neuronal functions. In the brains of the patients with Alzheimer's disease, distribution of clathrin was immunohistochemically investigated using four monoclonal antibodies against clathrin light chains, LCB.1, LCB.2, X-16 and CON.1, to study the involvement of clathrin in the pathology of Alzheimer's disease. LCB.1, LCB.2, X-16, and CON.1 bind to the aminoterminus of the clathrin light chain b(LCb), to the neuron-specific insert of LCb, to the light chain a(LCa), and to LCa and LCb, respectively. In Alzheimer brains, granular staining of LCB.2 around neurons in the hippocampus was weaker or patchily defected in comparison with control brains. Some neurofibrillary tangles and neurons were intensely stained in Alzheimer brains by LCB.2, whereas neurons were weakly stained in control brains. Crowns of some senile plaques in the brains of early onset Alzheimer's disease were positively stained by LCB. 2. LCB. 1 supported the observations of LCB.2. Reactive astrocytes in Alzheimer brains were intensely stained by X-16. On the other hand, Western blot analysis using LCB.2 and X-16 demonstrated no apparent differences in protein amounts and molecular weights of LCa and LCb between control and Alzheimer brains. These observations demonstrated abnormal distribution of clathrin in Alzheimer brains, implying impairment of axonal transport in this disease.
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Acton SL, Brodsky FM (1990) Predominance of clathrin light chain LCb correlates with the presence of a regulated secretory pathway. J Cell Biol 111: 1419–1426
Arai H, Schmidt ML, Lee VM-Y, Hurtig HI, Greenberg BD, Alder CH, Trojanowski JQ (1992) Epitope analysis of senile plaque components in the hippocampus of patients with Parkinson's disease. Neurology 42: 1315–1322
Black MM, Chestunt MH, Pleasure IT, Kenn JH (1991) Stable clathrin: uncoating protein (hsc70) complexes in intact neurons and their axonal transport. J Neurosci 11: 1163–1172
Blank SG, Brodsky FM (1986) Site-specific disruption of clathrin assembly produces novel structures. EMBO J 5: 2087–2095
Brodsky FM (1985) Clathrin structure characterized with monoclonal antibodies. 1. Analysis of multiple antigenic sites. J Cell Biol 101: 2047–2054
Brodsky FM (1985) Clathrin structure characterized with monoclonal antibodies. 2. Identification of in vivo forms of clathrin. J Cell Biol 101: 2055–2062
Brodsky FM (1988) Living with clathrin: its role in intracellular membrane traffic. Science 242: 1396–1402
Brodsky FM, Galloway CJ, Blank GS, Jackson AP, Seow H-F, Drickamer K, Parham P (1987) Localization of clathrin light-chain sequences mediating heavy-chain binding and coated vesicle diversity. Nature 326: 203–205
Brodsky FM, Hill BL, Acton SL, Näthke I, Wong DH, Ponnambalam S, Parham P (1991) Clathrin light chains: arrays of protein motifs that regulate coated-vesicle dynamics. Trends Biochm Sci 16: 208–213
Carner J, Lasek RJ (1981) Clathrin is axonally transported as a part of slow component b: the microfilament complex. J Cell Biol 88: 172–178
Chen WJ, Goldstein JS, Brown MJ (1990) NPXY, a sequence often found in cytoplasmic tails, is required for coated pitmediated internalization of the low density lipoprotein receptor. J Biol Chem 265: 3116–3123
de Waegh SM, Brady ST (1990) Slow axonal transport in Trembler mouse: altered cytoskeletal dynamics in a myelin deficient model. J Neurosci 10: 1855–1865
de Waegh SM, Lee VM-Y, Brady ST (1992) Local modulation of neurofilament phosphorylation, axonal caliber, and slow axonal transport by myelinating Schwann cells, Cell 68: 451–463
Doxsey SJ, Brodsky FM, Blank GS, Helenius A (1987) Inhibition of endocytosis by anti-clathrin antibodies. Cell 50: 453–463
Gower DJ, Tytell M (1987) Axonal transport of clathrin-associated proteins. Brain Res 407: 1–8
Haass C, Koo EH, Mellon A, Hung AY, Selkoe DJ (1992) Targeting of cell-surface beta-amyloid precursor protein to lysosomes: alternative processing into amyloid-bearing fragments. Nature 357: 500–503
Hanley MR, Selkoe DJ (1993) Amyloid precursor on the G0. Nature 362: 14–15
Heuser J (1989) The role of coated vesicles in recycling of synaptic vesicle membrane. Cell Biol Int Rep 13: 1063–1078
Jackson AP, Seow H-F Holmes N, Drickamer K, Parham P (1987) Clathrin light chains contain brain-specific insertion sequences and a region of homology with intermediate filaments. Science 326: 154–159
Kinnon C, Owen MJ (1983) Clathrin-coated vesicles purified from a human B lymphocyte cell line contain newly synthesized glycoproteins. J Biol Chem 258: 8470–8476
Lasek RJ, Garner JA, Brady ST (1984) Axonal transport of the cytoplasmic matrix. J Cell Biol 99: 212–221
Lemansky P, Hasilik A, von Figura K, Helmy S, Fishman J, Fine RE, Kedersha NL, Rome LH (1987) Lysosomal enzyme precursors in coated vesicles derived from exocytic and endocytic pathways. J Cell Biol 104: 1743–1748
Masliah E, Terry RD, DeTeresa RM, Hansen LA (1989) Immunohistochemical quantification of the synapse-related protein synaptophysin in Alzheimer disease. Neurosci Lett 103: 234–239
Masliah E, Terry RD, Alford M, DeTeresa RM, Hansen LA (1991) Cortical and subcortical patterns of synaptophysin-like immunoreactivity in Alzheimer's disease. Am J Pathol 138: 235–246
Maycox PR, Link E, Reetz A, Morris SA, Jahn R (1992) Clathrin-coated vesicles in nervous tissue are involved primarily in synaptic vesicle recycling. J Cell Biol 118: 1379–1388
McQuarrie IG, Brady ST, Lasek RJ (1989) Retardation in slow axonal transport of cytoskeletal elements during maturation and aging. Neurobiol Aging 10: 359–365
Nakamura Y, Takeda M, Suzuki H, Hattori H, Tada K, Hariguchi S, Hashimoto S, Nishimura T (1991) Abnormal distribution of cathepsins in the brain of patients with Alzheimer's discase. Neurosci Lett 130: 195–198
Näthke IS, Heuser J, Lupas A, Stock J, Truck CW, Brodsky FM (1992) Folding and trimerization of clathrin subunits at the triskelion hub. Cell 66: 899–910
Nishimoto I, Okamoto T, Matsuura Y, Takahashi S, Okamoto T, Murayama Y, Ogata E (1993) Alzheimer amyloid protein precursor complexes with brain GTP-binding protein G0. Nature 362: 75–79
Nordstedt C, Caporaso GL, Thyberg J, Gandy SE, Greengard (1993) Identification of the Alzheimer beta/A4 amyloid precursor protein in clathrin-coated vesicles purified from PC12 cells. J Biol Chem 268: 608–612
Standeart DG, Lee VM-Y, Greenberg BD, Lowery DE, Trojanowski JQ (1991) Molecular features of hypothalamic plaques in Alzheimer's disease. Am J Pathol 139: 681–691
Wong DH, Ignatius MJ, Parosky G, Parham P, Trojanowski JQ, Brodsky FM (1990) Neuron-specific expression of high-molecular-weight clathrin light chain. J Neurosci 10: 3025–3031
Yoshimi K, Takeda M, Nishimura T, Kudo T, Nakamura Y, Tada K, Iwata N (1991) An immunohistochemical study of MAP2 and clathrin in gerbil hippocampus after cerebral is-chemia. Brain Res 560: 149–158
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Nakamura, Y., Takeda, M., Yoshimi, K. et al. Involvement of clathrin light chains in the pathology of Alzheimer's disease. Acta Neuropathol 87, 23–31 (1994). https://doi.org/10.1007/BF00386251
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DOI: https://doi.org/10.1007/BF00386251