calsyntenin

{{Short description|Type of transmembrane protein}}

{{Infobox protein family

| Symbol = CLSTN

| Name = Calsyntenin

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| InterPro = IPR026914

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| Membranome family = 241

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Calsyntenins (Csts, CLSTN) are type I transmembrane proteins that belong to the cadherin superfamily. Their name comes from their ability to bind calcium. In birds and mammals, they consist of three family members (Cst1, 2 and 3),{{cite journal | vauthors = Vogt L, Schrimpf SP, Meskenaite V, Frischknecht R, Kinter J, Leone DP, Ziegler U, Sonderegger P | title = Calsyntenin-1, a proteolytically processed postsynaptic membrane protein with a cytoplasmic calcium-binding domain | journal = Mol. Cell. Neurosci. | volume = 17 | issue = 1 | pages = 151–66 |date=January 2001 | pmid = 11161476 | doi = 10.1006/mcne.2000.0937 | s2cid = 30856590 }}{{cite journal | vauthors = Hintsch G, Zurlinden A, Meskenaite V, Steuble M, Fink-Widmer K, Kinter J, Sonderegger P | title = The calsyntenins--a family of postsynaptic membrane proteins with distinct neuronal expression patterns | journal = Mol. Cell. Neurosci. | volume = 21 | issue = 3 | pages = 393–409 |date=November 2002 | pmid = 12498782 | doi = 10.1006/mcne.2002.1181| s2cid = 39530844 }} in nematodes one ortholog (CASY-1, originally CDH11) is known.{{cite journal | vauthors = Ikeda DD, Duan Y, Matsuki M, Kunitomo H, Hutter H, Hedgecock EM, Iino Y | title = CASY-1, an ortholog of calsyntenins/alcadeins, is essential for learning in Caenorhabditis elegans | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 105 | issue = 13 | pages = 5260–5 |date=April 2008 | pmid = 18381821 | pmc = 2278220 | doi = 10.1073/pnas.0711894105 | bibcode = 2008PNAS..105.5260I | doi-access = free }}

Cst1 (CLSTN1) was first shown to be predominantly expressed in postsynaptic membranes of excitatory neurons, Cst2 and 3 were found in an increased manner in inhibitory GABAergic neurons, in adult and embryonic tissue. Calsyntenins interact with numerous proteins such as with kinesin-1 and the APP-linker protein X11L/Mint2,{{cite journal | vauthors = Konecna A, Frischknecht R, Kinter J, Ludwig A, Steuble M, Meskenaite V, Indermühle M, Engel M, Cen C, Mateos JM, Streit P, Sonderegger P | title = Calsyntenin-1 docks vesicular cargo to kinesin-1 | journal = Mol. Biol. Cell | volume = 17 | issue = 8 | pages = 3651–63 | date = August 2006 | pmid = 16760430 | pmc = 1525238 | doi = 10.1091/mbc.E06-02-0112 | url = http://www.zora.uzh.ch/1134/1/KonecnaSonderegger2006V.pdf }}{{Dead link|date=November 2023 |bot=InternetArchiveBot |fix-attempted=yes }}{{cite journal | vauthors = Rindler MJ, Xu CF, Gumper I, Cen C, Sonderegger P, Neubert TA | title = Calsyntenins are secretory granule proteins in anterior pituitary gland and pancreatic islet alpha cells | journal = J. Histochem. Cytochem. | volume = 56 | issue = 4 | pages = 381–8 |date=April 2008 | pmid = 18158283 | pmc = 2326105 | doi = 10.1369/jhc.7A7351.2007 }} and were shown to have multi-purpose functions both within and outside the nervous system.{{cite journal | vauthors = Ludwig A, Blume J, Diep TM, Yuan J, Mateos JM, Leuthäuser K, Steuble M, Streit P, Sonderegger P | title = Calsyntenins mediate TGN exit of APP in a kinesin-1-dependent manner | journal = Traffic | volume = 10 | issue = 5 | pages = 572–89 |date=May 2009 | pmid = 19192245 | doi = 10.1111/j.1600-0854.2009.00886.x | s2cid = 205840816 | url = https://www.zora.uzh.ch/id/eprint/18250/2/Ludwig_et_al_2009V.pdf | doi-access = free }}

Shortly after the calsyntenins were discovered, they were found to regulate postsynaptic calcium concentration. Later it was found that another key-function is to link vesicles to kinesin light chain (KLC) and thus to co-determine transport of distinct cargo.{{cite journal | vauthors = Steuble M, Gerrits B, Ludwig A, Mateos JM, Diep TM, Tagaya M, Stephan A, Schätzle P, Kunz B, Streit P, Sonderegger P | title = Molecular characterization of a trafficking organelle: dissecting the axonal paths of calsyntenin-1 transport vesicles | journal = Proteomics | volume = 10 | issue = 21 | pages = 3775–88 |date=November 2010 | pmid = 20925061 | doi = 10.1002/pmic.201000384 | s2cid = 44660376 }} Recent studies identified a role for calsyntenin 1 in the regulation of vesicular trafficking of guidance receptors in dI1 axons at choice points.{{cite journal | doi = 10.1242/dev.127449 | title=Calsyntenin1-mediated trafficking of axon guidance receptors regulates the switch in axonal responsiveness at a choice point | year=2016 | journal=Development | vauthors=Alther TA, Domanitskaya E, Stoeckli ET }} In cooperation with RabGDI (Guanosine nucleotide dissociation inhibitor), calsyntenin 1 shuttles Rab11-positive vesicles containing Robo1 to the growth cone surface in a precisely regulated manner. By contrast, calsyntenin 1-mediated trafficking of frizzled 3, a guidance receptor in the Wnt pathway, is independent of RabGDI. Calsyntenin gene expression also elevates during oxidative stress in PC12 cells{{Cite journal |doi = 10.1016/j.gendis.2019.09.001|title = Elevation of gene expression of calcineurin, calmodulin and calsyntenin in oxidative stress induced PC12 cells|year = 2019|last1 = Aravind|first1 = P.|last2 = Bulbule|first2 = Sarojini R.|last3 = Hemalatha|first3 = N.|last4 = Babu|first4 = R.L.|last5 = Devaraju|first5 = K.S.|journal = Genes & Diseases|volume = 8|issue = 1|pages = 87–93|pmid = 33569517|pmc = 7859428|doi-access = free}}