Abstract
The sulfation of tyrosine residues is an important post-translational modification involved in the regulation of protein function. We examined the activity of worm tyrosylprotein sulfotransferase (TPST-1) on a typical cuticle collagen, ROL-6, in C. elegans. We verified that TPST-1 sulfates three tyrosine residues of ROL-6 in vitro. We found that these tyrosine residues are important for the secretion of ROL-6::GFP. Mutant ROL-6::GFP proteins that contain more than two substitutions of the target tyrosine residues are severely deficient in cuticle localization. Consistently, knock down of tpst-1 blocked the cuticle localization of ROL-6::GFP. Therefore, the sulfation of ROL-6 by TPST-1 is critical for the proper localization of ROL-6. We also confirmed that worm TPST-1 is localized to the trans-Golgi network (TGN). Our results indicate that TPST-1 regulates cuticle organization by promoting the transport of ROL-6 from the TGN to the cuticle.
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Baeuerle, P.A., and Huttner, W.B. (1985). Tyrosine sulfation of yolk proteins 1, 2, and 3 in Drosophila melanogaster. J. Biol. Chem. 260, 6434–6439.
Bard, F., Casano, L., Mallabiabarrena, A., Wallace, E., Saito, K., Kitayama, H., Guizzunti, G., Hu, Y., Wendler, F., Dasgupta, R., et al. (2006). Functional genomics reveals genes involved in protein secretion and Golgi organization. Nature 439, 604–607.
Beinfeld, M.C. (2003). Biosynthesis and processing of pro CCK: recent progress and future challenges. Life Sci. 72, 747–757.
Blott, S., Kim, J.J., Moisio, S., Schmidt-Kuntzel, A., Cornet, A., Berzi, P., Cambisano, N., Ford, C., Grisart, B., Johnson, D., et al. (2003). Molecular dissection of a quantitative trait locus: a phenylalanine-to-tyrosine substitution in the transmembrane domain of the bovine growth hormone receptor is associated with a major effect on milk yield and composition. Genetics 163, 253–266.
Borghei, A., Ouyang, Y.B., Westmuckett, A.D., Marcello, M.R., Landel, C.P., Evans, J.P., and Moore, K.L. (2006). Targeted disruption of tyrosylprotein sulfotransferase-2, an enzyme that catalyzes post-translational protein tyrosine O-sulfation, causes male infertility. J. Biol. Chem. 281, 9423–9431.
Brenner, S. (1974). The genetics of Caenorhabditis elegans. Genetics 77, 71–94.
Bundgaard, J.R., Vuust, J., and Rehfeld, J.F. (1995). Tyrosine Osulfation promotes proteolytic processing of progastrin. EMBO J. 14, 3073–3079.
Edens, W.A., Sharling, L., Cheng, G., Shapira, R., Kinkade, J.M., Lee, T., Edens, H.A., Tang, X., Sullards, C., Flaherty, D.B., et al. (2001). Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a multidomain oxidase/peroxidase with homology to the phagocyte oxidase subunit gp91phox. J. Cell Biol. 154, 879–891.
Friedman, L., Higgin, J.J., Moulder, G., Barstead, R., Raines, R.T., and Kimble, J. (2000). Prolyl 4-hydroxylase is required for viability and morphogenesis in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 97, 4736–4741.
Hammermeister, D.E., Serrano, J., Schmieder, P., and Kuehl, D.W. (2000). Characterization of dansylated glutathione, glutathione disulfide, cysteine and cystine by narrow bore liquid chromatography/electrospray ionization mass spectrometry. Rapid Commun. Mass Spectrom 14, 503–508.
Hanai, H., Nakayama, D., Yang, H., Matsubayashi, Y., Hirota, Y., and Sakagami, Y. (2000). Existence of a plant tyrosylprotein sulfotransferase: novel plant enzyme catalyzing tyrosine Osulfation of preprophytosulfokine variants in vitro. FEBS Lett. 470, 97–101.
Hobert, O., Mori, I., Yamashita, Y., Honda, H., Ohshima, Y., Liu, Y., and Ruvkun, G. (1997). Regulation of interneuron function in the C. elegans thermoregulatory pathway by the ttx-3 LIM homeobox gene. Neuron 19, 345–357.
Huttner, W.B. (1988). Tyrosine sulfation and the secretory pathway. Annu. Rev. Physiol. 50, 363–376.
Kamath, R.S., Martinez-Campos, M., Zipperlen, P., Fraser, A.G., and Ahringer, J. (2001). Effectiveness of specific RNA-mediated interference through ingested double-stranded RNA in Caenorhabditis elegans. Genome Biol. 2, RESEARCH0002.
Kehoe, J.W., and Bertozzi, C.R. (2000). Tyrosine sulfation: a modulator of extracellular protein-protein interactions. Chem. Biol. 7, R57–61.
Kim, T.H., Hwang, S.B., Jeong, P.Y., Lee, J., and Cho, J.W. (2005). Requirement of tyrosylprotein sulfotransferase-A for proper cuticle formation in the nematode C. elegans. FEBS Lett. 579, 53–58.
Ko, F.C., and Chow, K.L. (2002). A novel thioredoxin-like protein encoded by the C. elegans dpy-11 gene is required for body and sensory organ morphogenesis. Development 129, 1185–1194.
Kostidou, E., Koliakos, G., Paletas, K., and Kaloyianni, M. (2008). Monocyte attachment and migration through collagen IV in diabetes mellitus. Mol. Cells 25, 452–456.
Kramer, J.M., and Johnson, J.J. (1993). Analysis of mutations in the sqt-1 and rol-6 collagen genes of Caenorhabditis elegans. Genetics 135, 1035–1045.
Lee, R.W., and Huttner, W.B. (1983). Tyrosine-O-sulfated proteins of PC12 pheochromocytoma cells and their sulfation by a tyrosylprotein sulfotransferase. J. Biol. Chem. 258, 11326–11334.
Marchler-Bauer, A., and Bryant, S.H. (2004). CD-Search: protein domain annotations on the fly. Nucleic Acids Res. 32, W327–331.
Muller, L., Barret, A., Picart, R., and Tougard, C. (1997). Proteolytic processing of sulfated secretogranin II in the trans-Golgi network of GH3B6 prolactin cells. J. Biol. Chem. 272, 3669–3673.
Nemeth, J.F., Hochgesang, G.P., Jr., Marnett, L.J., and Caprioli, R.M. (2001). Characterization of the glycosylation sites in cyclooxygenase-2 using mass spectrometry. Biochemistry 40, 3109–3116.
Ouyang, Y.B., and Moore, K.L. (1998). Molecular cloning and expression of human and mouse tyrosylprotein sulfotransferase-2 and a tyrosylprotein sulfotransferase homologue in Caenorhabditis elegans. J. Biol. Chem. 273, 24770–24774.
Ouyang, Y.B., Crawley, J.T., Aston, C.E., and Moore, K.L. (2002). Reduced body weight and increased postimplantation fetal death in tyrosylprotein sulfotransferase-1-deficient mice. J. Biol. Chem. 277, 23781–23787.
Palnaes Hansen, C., Stadil, F., and Rehfeld, J.F. (2000). Metabolism and acid secretory effect of sulfated and nonsulfated gastrin-6 in humans. Am J. Physiol. Gastrointest. Liver Physiol. 279, G903–909.
Sasaki, N., Hosoda, Y., Nagata, A., Ding, M., Cheng, J.M., Miyamoto, T., Okano, S., Asano, A., Miyoshi, I., and Agui, T. (2007). A mutation in Tpst2 encoding tyrosylprotein sulfotransferase causes dwarfism associated with hypothyroidism. Mol. Endocrinol. 21, 1713–1721.
Westmuckett, A.D., Hoffhines, A.J., Borghei, A., and Moore, K.L. (2008). Early postnatal pulmonary failure and primary hypothyroidism in mice with combined TPST-1 and TPST-2 deficiency. Gen. Comp. Endocrinol. 156, 145–153.
Yang, J., and Kramer, J.M. (1994). In vitro mutagenesis of Caenorhabditis elegans cuticle collagens identifies a potential subtilisinlike protease cleavage site and demonstrates that carboxyl domain disulfide bonding is required for normal function but not assembly. Mol. Cell. Biol. 14, 2722–2730.
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Kim, T.H., Kim, D.H., Nam, H.W. et al. Tyrosylprotein sulfotransferase regulates collagen secretion in Caenorhabditis elegans . Mol Cells 29, 413–418 (2010). https://doi.org/10.1007/s10059-010-0049-4
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DOI: https://doi.org/10.1007/s10059-010-0049-4