Synaptophysin

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.

It is expressed in neuroendocrine cells and in virtually all neurons in the brain and spinal cord that participate in synaptic transmission.

The protein is a synaptic vesicle glycoprotein with four transmembrane domains weighing 38 kDa.

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.{{cite journal | vauthors = McMahon HT, Bolshakov VY, Janz R, Hammer RE, Siegelbaum SA, Südhof TC | title = Synaptophysin, a major synaptic vesicle protein, is not essential for neurotransmitter release | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 10 | pages = 4760–4764 | date = May 1996 | pmid = 8643476 | pmc = 39352 | doi = 10.1073/pnas.93.10.4760 | bibcode = 1996PNAS...93.4760M | doi-access = free }} 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.{{cite journal | vauthors = Schmitt U, Tanimoto N, Seeliger M, Schaeffel F, Leube RE | title = Detection of behavioral alterations and learning deficits in mice lacking synaptophysin | journal = Neuroscience | volume = 162 | issue = 2 | pages = 234–243 | date = August 2009 | pmid = 19393300 | doi = 10.1016/j.neuroscience.2009.04.046 | citeseerx = 10.1.1.320.5309 | s2cid = 16061817 }}

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.{{cite journal | vauthors = Calhoun ME, Jucker M, Martin LJ, Thinakaran G, Price DL, Mouton PR | title = Comparative evaluation of synaptophysin-based methods for quantification of synapses | journal = Journal of Neurocytology | volume = 25 | issue = 12 | pages = 821–828 | date = December 1996 | pmid = 9023727 | doi = 10.1007/BF02284844 | s2cid = 468594 }}

Using immunohistochemistry, synaptophysin can be demonstrated in a range of neural and neuroendocrine tissues,{{cite journal | vauthors = Wiedenmann B, Franke W, Kuhn C, Moll R, Gould V | title = Synaptophysin: a marker protein for neuroendocrine cells and neoplasms. | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 83 | issue = 10 | pages = 3500–3504 | date = May 1986 | pmid = 3010302 | pmc = 323544 | doi = 10.1073/pnas.83.10.3500 | bibcode = 1986PNAS...83.3500W | doi-access = free }} 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.{{cite book | vauthors = Leong AS, Cooper K, Leong FJ | title = Manual of Diagnostic Cytology | pages = 405–406 | year = 2003 | edition = 2 | publisher = Greenwich Medical Media, Ltd. | isbn = 978-1-84110-100-2 }}

Mutations in this gene have been implicated in X-linked intellectual disability.{{cite journal | vauthors = Tarpey PS, Smith R, Pleasance E, Whibley A, Edkins S, Hardy C, O'Meara S, Latimer C, Dicks E, Menzies A, Stephens P, Blow M, Greenman C, Xue Y, Tyler-Smith C, Thompson D, Gray K, Andrews J, Barthorpe S, Buck G, Cole J, Dunmore R, Jones D, Maddison M, Mironenko T, Turner R, Turrell K, Varian J, West S, Widaa S, Wray P, Teague J, Butler A, Jenkinson A, Jia M, Richardson D, Shepherd R, Wooster R, Tejada MI, Martinez F, Carvill G, Goliath R, de Brouwer AP, van Bokhoven H, Van Esch H, Chelly J, Raynaud M, Ropers HH, Abidi FE, Srivastava AK, Cox J, Luo Y, Mallya U, Moon J, Parnau J, Mohammed S, Tolmie JL, Shoubridge C, Corbett M, Gardner A, Haan E, Rujirabanjerd S, Shaw M, Vandeleur L, Fullston T, Easton DF, Boyle J, Partington M, Hackett A, Field M, Skinner C, Stevenson RE, Bobrow M, Turner G, Schwartz CE, Gecz J, Raymond FL, Futreal PA, Stratton MR | title = A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation | journal = Nature Genetics | volume = 41 | issue = 5 | pages = 535–543 | date = May 2009 | pmid = 19377476 | pmc = 2872007 | doi = 10.1038/ng.367 }}

Synaptophysin has been shown to interact with AP1G1{{cite journal | vauthors = Horikawa HP, Kneussel M, El Far O, Betz H | title = Interaction of synaptophysin with the AP-1 adaptor protein gamma-adaptin | journal = Molecular and Cellular Neurosciences | volume = 21 | issue = 3 | pages = 454–462 | date = November 2002 | pmid = 12498786 | doi = 10.1006/mcne.2002.1191 | s2cid = 54366866 }} and SIAH2.{{cite journal | vauthors = Wheeler TC, Chin LS, Li Y, Roudabush FL, Li L | title = Regulation of synaptophysin degradation by mammalian homologues of seven in absentia | journal = Journal of Biological Chemistry | volume = 277 | issue = 12 | pages = 10273–10282 | date = March 2002 | pmid = 11786535 | doi = 10.1074/jbc.M107857200 | doi-access = free }}

• List of human genes
• Merkel-cell carcinoma - although origin of this tumor is unclear, it does express synaptophysin

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• {{cite journal | vauthors = Kalina M, Lukinius A, Grimelius L, Höög A, Falkmer S | title = Ultrastructural localization of synaptophysin to the secretory granules of normal glucagon and insulin cells in human islets of Langerhans | journal = Ultrastructural Pathology | volume = 15 | issue = 3 | pages = 215–219 | year = 1991 | pmid = 1908157 | doi = 10.3109/01913129109021883 }}
• {{cite journal | vauthors = Ozçelik T, Lafreniere RG, Archer BT, Johnston PA, Willard HF, Francke U, Südhof TC | title = Synaptophysin: structure of the human gene and assignment to the X chromosome in man and mouse | journal = American Journal of Human Genetics | volume = 47 | issue = 3 | pages = 551–561 | date = Sep 1990 | pmid = 1975480 | pmc = 1683862 }}
• {{cite journal | vauthors = Goto S, Hirano A, Pearson J | title = Calcineurin and synaptophysin in the human spinal cord of normal individuals and patients with familial dysautonomia | journal = Acta Neuropathologica | volume = 79 | issue = 6 | pages = 647–652 | year = 1990 | pmid = 2163183 | doi = 10.1007/BF00294243 | s2cid = 51685991 }}
• {{cite journal | vauthors = de Koning JP, Schelen AM, Dong F, van Buitenen C, Burgering BM, Bos JL, Löwenberg B, Touw IP | title = Specific involvement of tyrosine 764 of human granulocyte colony-stimulating factor receptor in signal transduction mediated by p145/Shc/GRB2 or p90/GRB2 complexes | journal = Blood | volume = 87 | issue = 1 | pages = 132–140 | date = Jan 1996 | pmid = 8547634 | doi = 10.1182/blood.V87.1.132.132 | doi-access = free }}
• {{cite journal | vauthors = Zhang PJ, Rosenblum MK | title = Synaptophysin expression in the human spinal cord. Diagnostic implications of an immunohistochemical study | journal = The American Journal of Surgical Pathology | volume = 20 | issue = 3 | pages = 273–276 | date = Mar 1996 | pmid = 8772779 | doi = 10.1097/00000478-199603000-00002 }}
• {{cite journal | vauthors = Bouwens L, Lu WG, De Krijger R | title = Proliferation and differentiation in the human fetal endocrine pancreas | journal = Diabetologia | volume = 40 | issue = 4 | pages = 398–404 | date = Apr 1997 | pmid = 9112016 | doi = 10.1007/s001250050693 | doi-access = free }}
• {{cite journal | vauthors = Fisher SE, Ciccodicola A, Tanaka K, Curci A, Desicato S, D'urso M, Craig IW | title = Sequence-based exon prediction around the synaptophysin locus reveals a gene-rich area containing novel genes in human proximal Xp | journal = Genomics | volume = 45 | issue = 2 | pages = 340–347 | date = Oct 1997 | pmid = 9344658 | doi = 10.1006/geno.1997.4941 | hdl = 11858/00-001M-0000-0012-CBE6-7 | hdl-access = free }}
• {{cite journal | vauthors = Maggiano N, Lauriola L, Serra FG, Ricci R, Capelli A, Ranelletti FO | title = Detection of synaptophysin-producing cells in human thymus by immunohistochemistry and nonradioactive in situ hybridization | journal = The Journal of Histochemistry and Cytochemistry| volume = 47 | issue = 2 | pages = 237–243 | date = Feb 1999 | pmid = 9889259 | doi = 10.1177/002215549904700212 | doi-access = free }}
• {{cite journal | vauthors = Portela-Gomes GM, Stridsberg M, Johansson H, Grimelius L | title = Co-localization of synaptophysin with different neuroendocrine hormones in the human gastrointestinal tract | journal = Histochemistry and Cell Biology | volume = 111 | issue = 1 | pages = 49–54 | date = Jan 1999 | pmid = 9930883 | doi = 10.1007/s004180050332 | s2cid = 24958759 }}
• {{cite journal | vauthors = Davidsson P, Gottfries J, Bogdanovic N, Ekman R, Karlsson I, Gottfries CG, Blennow K | title = The synaptic-vesicle-specific proteins rab3a and synaptophysin are reduced in thalamus and related cortical brain regions in schizophrenic brains | journal = Schizophrenia Research | volume = 40 | issue = 1 | pages = 23–29 | date = Nov 1999 | pmid = 10541003 | doi = 10.1016/S0920-9964(99)00037-7 | s2cid = 22059000 }}
• {{cite journal | vauthors = Cassiman D, van Pelt J, De Vos R, Van Lommel F, Desmet V, Yap SH, Roskams T | title = Synaptophysin: A Novel Marker for Human and Rat Hepatic Stellate Cells | journal = The American Journal of Pathology | volume = 155 | issue = 6 | pages = 1831–1839 | date = Dec 1999 | pmid = 10595912 | pmc = 1866940 | doi = 10.1016/S0002-9440(10)65501-0 }}
• {{cite journal | vauthors = Thiele C, Hannah MJ, Fahrenholz F, Huttner WB | title = Cholesterol binds to synaptophysin and is required for biogenesis of synaptic vesicles | journal = Nature Cell Biology | volume = 2 | issue = 1 | pages = 42–49 | date = Jan 2000 | pmid = 10620806 | doi = 10.1038/71366 | s2cid = 2623757 }}
• {{cite journal | vauthors = Nag TC, Wadhwa S | title = Differential expression of syntaxin-1 and synaptophysin in the developing and adult human retina | journal = Journal of Biosciences | volume = 26 | issue = 2 | pages = 179–191 | date = Jun 2001 | pmid = 11426054 | doi = 10.1007/BF02703642 | s2cid = 2178765 }}
• {{cite journal | vauthors = Bhangu PS, Genever PG, Spencer GJ, Grewal TS, Skerry TM | title = Evidence for targeted vesicular glutamate exocytosis in osteoblasts | journal = Bone | volume = 29 | issue = 1 | pages = 16–23 | date = Jul 2001 | pmid = 11472886 | doi = 10.1016/S8756-3282(01)00482-3 }}
• {{cite journal | vauthors = Roudenok V, Kühnel W | title = The development of synaptophysin immunoreactivity in the human sympathetic ganglia | journal = Annals of Anatomy = Anatomischer Anzeiger| volume = 183 | issue = 4 | pages = 345–351 | date = Jul 2001 | pmid = 11508360 | doi = 10.1016/S0940-9602(01)80177-1 }}
• {{cite journal | vauthors = Wheeler TC, Chin LS, Li Y, Roudabush FL, Li L | title = Regulation of synaptophysin degradation by mammalian homologues of seven in absentia | journal = Journal of Biological Chemistry | volume = 277 | issue = 12 | pages = 10273–10282 | date = Mar 2002 | pmid = 11786535 | doi = 10.1074/jbc.M107857200 | doi-access = free }}
• {{cite journal | vauthors = Ulfig N, Chan WY | title = Expression of a kinase anchoring protein 79 and synaptophysin in the developing human red nucleus | journal = Neuro-Signals | volume = 11 | issue = 2 | pages = 95–102 | year = 2003 | pmid = 12077483 | doi = 10.1159/000058546 | s2cid = 46792009 }}
• {{cite journal | vauthors = Yao I, Iida J, Nishimura W, Hata Y | title = Synaptic and nuclear localization of brain-enriched guanylate kinase-associated protein | journal = The Journal of Neuroscience| volume = 22 | issue = 13 | pages = 5354–5364 | date = Jul 2002 | pmid = 12097487 | pmc = 6758191 | doi = 10.1523/JNEUROSCI.22-13-05354.2002 }}
• {{cite journal | vauthors = Wistow G, Bernstein SL, Wyatt MK, Ray S, Behal A, Touchman JW, Bouffard G, Smith D, Peterson K | title = 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 | journal = Molecular Vision | volume = 8 | pages = 196–204 | date = Jun 2002 | pmid = 12107411 }}

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• {{MeshName|Synaptophysin}}

{{Tumor markers}}

{{Nerve tissue protein}}

Category:Glycoproteins

Category:Tumor markers