Synucleins belong to a family of small soluble proteins with chaperonic activity implicated in human diseases, but their normal function is not completely understood. Expression of ?, ? and ?-synucleins was analyzed in rat and human lens on different stages of development. No significant expression of ?- and ?-synucleins were found, whereas ?-synuclein was expressed in both species only on early stages of lens development. Examination of ?-synuclein upstream region demonstrated the similarity in its organization with promoter regions of crystallins and heat shock protein’s genes. ?-Synuclein upstream region contains motives identical or similar to regulatory cis-elements in their promoters including binding sites for Pax6 and Sox. These results suggest that ?-synuclein plays a role in distinct temporal events in lens development, presumably acting as a specific chaperone.
Macario, A.J. and de Macario, E.C. (2007) Molecular chaperones: Multiple functions, pathologies, and potential applications. Frontiers in Bioscience, 12, 2588-2600.
Quinlan, R. (2002) Cytoskeletal competence requires protein chaperones. Progress in Molecular and Subcel-lular Biology, 28, 219-233.
Nagai, N., Hosokawa, M., Itohara, S., Adachi, E., Mat-sushita, T., Hosokawa, N., et al. (2000) Embryonic le-thality of molecular chaperone Hsp47 knockout mice is associated with defects in collagen biosynthesis. Journal of Cell Biology, 150(6), 1499-1506.
Dix, D.J., Allen, J.W., Collins, B.W., Mori, C., Nakamura, N., Poorman-Allen, P., et al. (1996) Targeted gene dis-ruption of Hsp70-2 results in failed meiosis, germ cell apoptosis, and male infertility. Proceedings of the National Academy of Sciences of the United States of America, 93(8), 3264-3268.
Evans, T.G., Yamamoto, Y., Jeffery, W.R. and Krone, P.H. (2005) Zebrafish Hsp70 is required for embryonic lens formation. Cell Stress and Chaperones, 10(1), 66-78.
Souza, J.M., Giasson, B.I., Leeb, V.M. and Ischiropoulo-sa, H. (2000) Chaperone-like activity of synucleins. FEBS Letters, 474(1), 116-119.
Surgucheva, I., Ninkina, N., Buchman, V.L., Grasing, K. and Surguchov, A. (2005) Protein aggregation in retinal cells and approaches to cell protection. Cellular and Mo-lecular Neurobiology, 25(6), 1051-1066.
Surguchov, A. (2008) Molecular and cellular biology of synucleins. International Review of Cell and Molecular Biology, 270, 225-317.
Perrin, R.J., Woods, W.S., Clayton, D.F. and George, J.M. (2002) Interaction of human alpha-Synuclein and Par-kinson’s disease variants with phospholipids. Structural analysis using site-directed mutagenesis. Journal of Bio-logical Chemistry, 275(44), 34393-34398.
Smith, D.P., Tew, D.J., Hill, A.F., Bottomley, S.P., Mas-ters, C.L., Barnham, K.J., et al. (2008) Formation of a high affinity lipid-binding intermediate during the early aggregation phase of alpha-synuclein. Biochemistry, 47(5), 1425-1434.
Ltic, S., Perovic, M., Mladenovic, A., Raicevic, N., Ruz-dijic, S., Rakic, L., et al. (2004) Alpha-synuclein is ex-pressed in different tissues during human fetal develop-ment. Journal of Molecular Neuroscience, 22(3), 199-204.
Raghavan, R., Kruijff, L., Sterrenburg, M.D., Rogers, B.B., Hladik, C.L. and White, C.L. III (2004) Alpha- synuclein expression in the developing human brain. Pe-diatric and Developmental Pathology, 7(5), 506-516.
Buchman, V.L., Hunter, H.J., Pin?n, L.G., Thompson, J., Privalova, E.M., Ninkina, N.N., et al. (1998) Persyn, a member of the synuclein family, has a distinct pattern of expression in the developing nervous system. Journal of Neuroscience, 18(22), 9335-9341.
Surguchov, A., McMahon, B., Masliah, E. and Surgu-cheva, I. (2001) Synucleins in ocular tissues. Journal of Neuroscience Research, 65(1), 68-77.
Blechinger, S.R., Evans, T.G., Tang, P.T., Kuwada, J.Y., Warren, J.T. Jr. and Krone, P.H. (2002) The heat-inducible zebrafish Hsp70 gene is expressed during normal lens development under non-stress conditions. Mechanisms of Development, 112(1-2), 213-215.
Boyle, D.L., Takemoto, L., Brady, J.P. and Wawrousek, E.F. (2003) Morphological characterization of the Alpha A- and Alpha B-crystallin double knockout mouse lens. BMC Ophthalmology, 3(3), 1-11.
Tallot, P., Grongnet, J.F. and David, J.C. (2003) Dual perinatal and developmental expression of the small heat shock proteins aB-crystallin and Hsp27 in different tissues of the developing piglet. Biology of the Neonate, 83(4), 281-288.
Chenna, R., Sugawara, H., Koike, T., Lopez, R., Gibson, T.J., Higgins, D.G., et al. (2003) Multiple sequence alignment with the Clustal series of programs. Nucleic Acids Research, 31(13), 3497-3500.
Nakamura, T., Donovan, D.M., Hamada, K., Sax, C.M., Norman, B., Flanagan, J.R., et al. (1990) Regulation of the mouse alpha A-crystallin gene: Isolation of a cDNA encoding a protein that binds to a cis sequence motif shared with the major histocompatibility complex class I gene and other genes. Molecular and Cellular Biology, 10(7), 3700-3708.
Jaworski, C.J., Chepelinsky, A.B. and Piatigorsky, J. (1991) The alpha A-crystallin gene: Conserved features of the 5’-flanking regions in human, mouse, and chicken. Journal of Molecular Evolution, 33(6), 495-505.
Klement, J.F., Cvekl, A. and Piatigorsky, J. (1993) Func-tional elements DE2A, DE2B, and DE1A and the TATA box are required for activity of the chicken alpha A-crys- tallin gene in transfected lens epithelial cells. Journal of Biological Chemistry, 268, 6777-6784.
Mizuno, N., Ueda, Y. and Kondoh, H. (2005) Require-ment for betaB1-crystallin promoter of Xenopus laevis in embryonic lens development and lens regeneration. De-velopment, Growth and Differentiation, 47(3), 131-140.
Cui, W., Tomarev, S.I., Piatigorsky, J., Chepelinsky, A.B. and Duncan, M.K. (2004) Mafs, Prox1, and Pax6 can re-gulate chicken betaB1-crystallin gene expression. Journal of Biological Chemistry, 279(12), 11088-11095.
Epstein, J., Cai, J., Glaser, T., Jepeal, L. and Maas, R. (1994) Identification of a Pax paired domain recognition sequence and evidence for DNA-dependent conforma-tional changes. Journal of Biological Chemistry, 269(11), 8355-8361.
Zhou, Y.H., Zheng, J.B., Gu, X., Saunders, G.F. and Yung, W.K. (2002) Novel Pax6 binding sites in the human genome and the role of repetitive elements in the evolution of gene regulation. Genome Research, 12(11), 1716-1722.
Amin, J., Ananthan, J. and Voellmy, R. (1988) Key fea-tures of heat shock regulatory elements. Molecular and Cellular Biology, 8(9), 3761-3769.
Perisic, O., Xiao, H. and Lis, J.T. (1989) Stable binding of Drosophila heat shock factor to head-to-head and tail-to-tail repeats of a conserved 5 bp recognition unit. Cell, 59(5), 797-806.
Yasuda, K., Ishihara, K., Nakashima, K. and Hatayama, T. (1999) Genomic cloning and promoter analysis of the mouse 105-kDa heat shock protein (HSP105) gene. Bio-chemical and Biophysical Research Communications, 256(1), 75-80.
Van Heyningen, V. and Williamson, K.A. (2002) Pax6 in sensory development. Human Molecular Genetics, 11(10), 1161-1167.
Kamachi, Y., Uchikawa, M., Tanouchi, A., Sekido, R. and Kondoh, H. (2001) Pax6 and SOX2 form a co-DNA-binding partner complex that regulates initiation of lens development. Genes and Development, 15(10), 272-286.
Lengler, J., Bittner, T., Münster, D., Gawad, A.-D. and Graw, J. (2005) Agonistic and antagonistic action of AP2, Msx2, Pax6, Prox1 AND Six3 in the regulation of Sox2 expression. Ophthalmic Research, 37(6), 301-309.
Yang, Y., Stopka, T., Golestaneh, N., Wang, Y., Wu, K., Li, A., et al. (2006) Regulation of alphaA-crystallin via Pax6, c-Maf, CREB and a broad domain of lens-specific chromatin. EMBO Journal, 25(10), 2107-2118.
Muta, M., Kamachi, Y., Yoshimoto, A., Higashi, Y. and Kondoh, H. (2002) Distinct roles of SOX2, Pax6 and Maf transcription factors in the regulation of lens-specific delta1-crystallin enhancer. Genes to Cells, 7(8), 791-805.
Chen, X., Taube, J.R., Simirskii, V.I., Patel, T.P. and Duncan, M.K. (2008) Dual roles for Prox1 in the regula-tion of the chicken betaB1-crystallin promoter. Investiga-tive Ophthalmology & Visual Science, 49(4), 1542-1552.
Kerppola, T.K. and Curran, T. (1994) Maf and Nrl can bind to AP-1 sites and form heterodimers with Fos and Jun. Oncogene, 9(3), 675-684.
Mahoney, K.M., Petrovic, N., Schacke, W. and Shapiro, L.H. (2007) CD13/APN transcription is regulated by the proto-oncogene c-Maf via an atypical response element. Gene, 403(1-2), 178-187.
Lu, A., Gupta, A., Li, C., Ahlborn, T.E., Ma, Y., Shi, E.Y., et al. (2001) Molecular mechanisms for aberrant expres-sion of the human breast cancer specific gene 1 in breast cancer cells: control of transcription by DNA methylation and intronic sequences. Oncogene, 20(37), 5173-5185.
Grinchuk, O., Kozmik, Z., Wu, X. and Tomarev, S. (2005) The Optimedin gene is a downstream target of Pax6. Journal of Biological Chemistry, 280(10), 35228-35237.
Jia, T., Liu, Y.E., Liu, J. and Shi, Y.E. (1999) Stimulation of breast cancer invasion and metastasis by synuclein gamma. Cancer Research, 59(3), 742-747.
Gupta, A., Inaba, S., Wong, O.K., Fang, G. and Liu, J. (2003) Breast cancer-specific gene 1 interacts with the mitotic checkpoint kinase BubR1. Oncogene, 22(48), 7593-7599.
Wride, M.A. (1996) Cellular and molecular features of lens differentiation: a review of recent advances. Diffe-rentiation, 61(2), 77-93.
Ninkina, N.N., Privalova, E.M., Pinon, L.G., Davies, A.M. and Buchman, V.L. (1999) Developmentally regulated expression of persyn, a member of the synuclein family, in skin. Experimental Cell Research, 246(2), 308- 311.
Brady, J.P., Garland, D.L., Green, D.E., Tamm, E.R., Gib- lin, F.J. and Wawrousek, E.F. (2001) AlphaB-crystallin in lens development and muscle integrity: A gene knockout approach. Investigative Ophthalmology & Visual Science, 42(12), 2924-2934.
Wride, M.A. (2000) Minireview: Apoptosis as seen through a lens. Apoptosis, 5(3), 203-209.
Surgucheva, I. and Surguchov, A. (2008) γ-synuclein: Cell-type-specific promoter activity and binding to tran-scription factors. Journal of Molecular Neuroscience, 35(3), 267-271.
Akil, O., Weber, C.M., Park, S.N., Ninkina, N.N., Buch-man, V.L. and Lustig, L.R. (2008) Localization of synuc-leins in the mammalian cochlea. Journal of the Association for Research in Otolaryngology, 9(4), 452-463.
Muchowski, P.J., Ramsden, R., Nguyen, Q., Arnett, E.E., Greiling, T.M., Anderson, S.K., et al. (2008) Noninvasive measurement of protein aggregation by mutant huntingtin fragments or alpha-synuclein in the lens. Journal of Biological Chemistry, 283(10), 6330-6336.