Synaptophysin
Synaptophysin, also known as the major synaptic vesicle protein p38, is a protein that in humans is encoded by the SYP gene.[5][6]
Gene
The gene is located on the short arm of X chromosome (Xp11.23-p11.22). It is 12,406 bases in length and lies on the minus strand.
Tissue distribution
It is expressed in neuroendocrine cells and in virtually all neurons in the brain and spinal cord that participate in synaptic transmission.
Structure
The protein is a synaptic vesicle glycoprotein with four transmembrane domains weighing 38 kDa.
Function
The exact function of the protein is unknown: it interacts with the essential synaptic vesicle protein synaptobrevin, but when the synaptophysin gene is experimentally inactivated in animals, they still develop and function normally.[7] Recent research has shown, however, that elimination of synaptophysin in mice creates behavioral changes such as increased exploratory behavior, impaired object novelty recognition, and reduced spatial learning.[8]
Clinical significance
Biomarker
It acts as a marker for neuroendocrine tumors, and its ubiquity at the synapse has led to the use of synaptophysin immunostaining for quantification of synapses.[9]
Using immunohistochemistry, synaptophysin can be demonstrated in a range of neural and neuroendocrine tissues,[10] including cells of the adrenal medulla and pancreatic islets. As a specific marker for these tissues, it can be used to identify tumours arising from them, such as neuroblastoma, retinoblastoma, phaeochromocytoma, carcinoid, small-cell carcinoma, medulloblastoma and medullary thyroid carcinoma, among others. Diagnostically, it is often used in combination with chromogranin A.[11]
X-linked intellectual disability
Mutations in this gene have been implicated in X-linked intellectual disability.[12]
Interactions
Synaptophysin has been shown to interact with AP1G1[13] and SIAH2.[14]
See also
- List of human genes
- Merkel-cell carcinoma - although origin of this tumor is unclear, it does express synaptophysin
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000102003 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031144 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: SYP synaptophysin".
- ^ Südhof TC, Lottspeich F, Greengard P, Mehl E, Jahn R (November 1987). "The cDNA and derived amino acid sequences for rat and human synaptophysin". Nucleic Acids Research. 15 (22): 9607. doi:10.1093/nar/15.22.9607. PMC 306499. PMID 3120152.
- ^ McMahon HT, Bolshakov VY, Janz R, Hammer RE, Siegelbaum SA, Südhof TC (May 1996). "Synaptophysin, a major synaptic vesicle protein, is not essential for neurotransmitter release". Proceedings of the National Academy of Sciences of the United States of America. 93 (10): 4760–4764. Bibcode:1996PNAS...93.4760M. doi:10.1073/pnas.93.10.4760. PMC 39352. PMID 8643476.
- ^ Schmitt U, Tanimoto N, Seeliger M, Schaeffel F, Leube RE (August 2009). "Detection of behavioral alterations and learning deficits in mice lacking synaptophysin". Neuroscience. 162 (2): 234–243. CiteSeerX 10.1.1.320.5309. doi:10.1016/j.neuroscience.2009.04.046. PMID 19393300. S2CID 16061817.
- ^ Calhoun ME, Jucker M, Martin LJ, Thinakaran G, Price DL, Mouton PR (December 1996). "Comparative evaluation of synaptophysin-based methods for quantification of synapses". Journal of Neurocytology. 25 (12): 821–828. doi:10.1007/BF02284844. PMID 9023727. S2CID 468594.
- ^ Wiedenmann B, Franke W, Kuhn C, Moll R, Gould V (May 1986). "Synaptophysin: a marker protein for neuroendocrine cells and neoplasms". Proceedings of the National Academy of Sciences of the United States of America. 83 (10): 3500–3504. Bibcode:1986PNAS...83.3500W. doi:10.1073/pnas.83.10.3500. PMC 323544. PMID 3010302.
- ^ Leong AS, Cooper K, Leong FJ (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd. pp. 405–406. ISBN 978-1-84110-100-2.
- ^ Tarpey PS, Smith R, Pleasance E, Whibley A, Edkins S, Hardy C, et al. (May 2009). "A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation". Nature Genetics. 41 (5): 535–543. doi:10.1038/ng.367. PMC 2872007. PMID 19377476.
- ^ Horikawa HP, Kneussel M, El Far O, Betz H (November 2002). "Interaction of synaptophysin with the AP-1 adaptor protein gamma-adaptin". Molecular and Cellular Neurosciences. 21 (3): 454–462. doi:10.1006/mcne.2002.1191. PMID 12498786. S2CID 54366866.
- ^ Wheeler TC, Chin LS, Li Y, Roudabush FL, Li L (March 2002). "Regulation of synaptophysin degradation by mammalian homologues of seven in absentia". Journal of Biological Chemistry. 277 (12): 10273–10282. doi:10.1074/jbc.M107857200. PMID 11786535.
Further reading
- Kalina M, Lukinius A, Grimelius L, Höög A, Falkmer S (1991). "Ultrastructural localization of synaptophysin to the secretory granules of normal glucagon and insulin cells in human islets of Langerhans". Ultrastructural Pathology. 15 (3): 215–219. doi:10.3109/01913129109021883. PMID 1908157.
- Ozçelik T, Lafreniere RG, Archer BT, Johnston PA, Willard HF, Francke U, et al. (Sep 1990). "Synaptophysin: structure of the human gene and assignment to the X chromosome in man and mouse". American Journal of Human Genetics. 47 (3): 551–561. PMC 1683862. PMID 1975480.
- Goto S, Hirano A, Pearson J (1990). "Calcineurin and synaptophysin in the human spinal cord of normal individuals and patients with familial dysautonomia". Acta Neuropathologica. 79 (6): 647–652. doi:10.1007/BF00294243. PMID 2163183. S2CID 51685991.
- de Koning JP, Schelen AM, Dong F, van Buitenen C, Burgering BM, Bos JL, et al. (Jan 1996). "Specific involvement of tyrosine 764 of human granulocyte colony-stimulating factor receptor in signal transduction mediated by p145/Shc/GRB2 or p90/GRB2 complexes". Blood. 87 (1): 132–140. doi:10.1182/blood.V87.1.132.132. PMID 8547634.
- Zhang PJ, Rosenblum MK (Mar 1996). "Synaptophysin expression in the human spinal cord. Diagnostic implications of an immunohistochemical study". The American Journal of Surgical Pathology. 20 (3): 273–276. doi:10.1097/00000478-199603000-00002. PMID 8772779.
- Bouwens L, Lu WG, De Krijger R (Apr 1997). "Proliferation and differentiation in the human fetal endocrine pancreas". Diabetologia. 40 (4): 398–404. doi:10.1007/s001250050693. PMID 9112016.
- Fisher SE, Ciccodicola A, Tanaka K, Curci A, Desicato S, D'urso M, et al. (Oct 1997). "Sequence-based exon prediction around the synaptophysin locus reveals a gene-rich area containing novel genes in human proximal Xp". Genomics. 45 (2): 340–347. doi:10.1006/geno.1997.4941. hdl:11858/00-001M-0000-0012-CBE6-7. PMID 9344658.
- Maggiano N, Lauriola L, Serra FG, Ricci R, Capelli A, Ranelletti FO (Feb 1999). "Detection of synaptophysin-producing cells in human thymus by immunohistochemistry and nonradioactive in situ hybridization". The Journal of Histochemistry and Cytochemistry. 47 (2): 237–243. doi:10.1177/002215549904700212. PMID 9889259.
- Portela-Gomes GM, Stridsberg M, Johansson H, Grimelius L (Jan 1999). "Co-localization of synaptophysin with different neuroendocrine hormones in the human gastrointestinal tract". Histochemistry and Cell Biology. 111 (1): 49–54. doi:10.1007/s004180050332. PMID 9930883. S2CID 24958759.
- Davidsson P, Gottfries J, Bogdanovic N, Ekman R, Karlsson I, Gottfries CG, et al. (Nov 1999). "The synaptic-vesicle-specific proteins rab3a and synaptophysin are reduced in thalamus and related cortical brain regions in schizophrenic brains". Schizophrenia Research. 40 (1): 23–29. doi:10.1016/S0920-9964(99)00037-7. PMID 10541003. S2CID 22059000.
- Cassiman D, van Pelt J, De Vos R, Van Lommel F, Desmet V, Yap SH, et al. (Dec 1999). "Synaptophysin: A Novel Marker for Human and Rat Hepatic Stellate Cells". The American Journal of Pathology. 155 (6): 1831–1839. doi:10.1016/S0002-9440(10)65501-0. PMC 1866940. PMID 10595912.
- Thiele C, Hannah MJ, Fahrenholz F, Huttner WB (Jan 2000). "Cholesterol binds to synaptophysin and is required for biogenesis of synaptic vesicles". Nature Cell Biology. 2 (1): 42–49. doi:10.1038/71366. PMID 10620806. S2CID 2623757.
- Nag TC, Wadhwa S (Jun 2001). "Differential expression of syntaxin-1 and synaptophysin in the developing and adult human retina". Journal of Biosciences. 26 (2): 179–191. doi:10.1007/BF02703642. PMID 11426054. S2CID 2178765.
- Bhangu PS, Genever PG, Spencer GJ, Grewal TS, Skerry TM (Jul 2001). "Evidence for targeted vesicular glutamate exocytosis in osteoblasts". Bone. 29 (1): 16–23. doi:10.1016/S8756-3282(01)00482-3. PMID 11472886.
- Roudenok V, Kühnel W (Jul 2001). "The development of synaptophysin immunoreactivity in the human sympathetic ganglia". Annals of Anatomy = Anatomischer Anzeiger. 183 (4): 345–351. doi:10.1016/S0940-9602(01)80177-1. PMID 11508360.
- Wheeler TC, Chin LS, Li Y, Roudabush FL, Li L (Mar 2002). "Regulation of synaptophysin degradation by mammalian homologues of seven in absentia". Journal of Biological Chemistry. 277 (12): 10273–10282. doi:10.1074/jbc.M107857200. PMID 11786535.
- Ulfig N, Chan WY (2003). "Expression of a kinase anchoring protein 79 and synaptophysin in the developing human red nucleus". Neuro-Signals. 11 (2): 95–102. doi:10.1159/000058546. PMID 12077483. S2CID 46792009.
- Yao I, Iida J, Nishimura W, Hata Y (Jul 2002). "Synaptic and nuclear localization of brain-enriched guanylate kinase-associated protein". The Journal of Neuroscience. 22 (13): 5354–5364. doi:10.1523/JNEUROSCI.22-13-05354.2002. PMC 6758191. PMID 12097487.
- Wistow G, Bernstein SL, Wyatt MK, Ray S, Behal A, Touchman JW, et al. (Jun 2002). "Expressed sequence tag analysis of human retina for the NEIBank Project: retbindin, an abundant, novel retinal cDNA and alternative splicing of other retina-preferred gene transcripts". Molecular Vision. 8: 196–204. PMID 12107411.
External links
- Synaptophysin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)