Calsyntenin Explained

Symbol:	CLSTN
Calsyntenin
Interpro:	IPR026914
Membranome Family:	241

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),^{[1] [2]} in nematodes one ortholog (CASY-1, originally CDH11) is known.^[3]

Cst1 (CLSTN1) was first shown to be predominantly expressed in postsynaptic membranes of excitatory neurons,^[1] Cst2 and 3 were found in an increased manner in inhibitory GABAergic neurons,^[2] in adult and embryonic tissue. Calsyntenins interact with numerous proteins such as with kinesin-1 and the APP-linker protein X11L/Mint2,^{[4] [5]} and were shown to have multi-purpose functions both within and outside the nervous system.^{[3] [4] [5] [6]}

Shortly after the calsyntenins were discovered, they were found to regulate postsynaptic calcium concentration.^[1] 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.^{[4] [7]} Recent studies identified a role for calsyntenin 1 in the regulation of vesicular trafficking of guidance receptors in dI1 axons at choice points.^[8] 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^[9]

External links

• Web site: The calsyntenin family of postsynaptic membrane proteins . Universität Zürich .

Notes and References

1. Vogt L, Schrimpf SP, Meskenaite V, Frischknecht R, Kinter J, Leone DP, Ziegler U, Sonderegger P . Calsyntenin-1, a proteolytically processed postsynaptic membrane protein with a cytoplasmic calcium-binding domain . Mol. Cell. Neurosci. . 17 . 1 . 151–66 . January 2001 . 11161476 . 10.1006/mcne.2000.0937 . 30856590 .
2. Hintsch G, Zurlinden A, Meskenaite V, Steuble M, Fink-Widmer K, Kinter J, Sonderegger P . The calsyntenins--a family of postsynaptic membrane proteins with distinct neuronal expression patterns . Mol. Cell. Neurosci. . 21 . 3 . 393–409 . November 2002 . 12498782 . 10.1006/mcne.2002.1181. 39530844 .
3. Ikeda DD, Duan Y, Matsuki M, Kunitomo H, Hutter H, Hedgecock EM, Iino Y . CASY-1, an ortholog of calsyntenins/alcadeins, is essential for learning in Caenorhabditis elegans . Proc. Natl. Acad. Sci. U.S.A. . 105 . 13 . 5260–5 . April 2008 . 18381821 . 2278220 . 10.1073/pnas.0711894105 . 2008PNAS..105.5260I . free .
4. Konecna A, Frischknecht R, Kinter J, Ludwig A, Steuble M, Meskenaite V, Indermühle M, Engel M, Cen C, Mateos JM, Streit P, Sonderegger P . Calsyntenin-1 docks vesicular cargo to kinesin-1 . Mol. Biol. Cell . 17 . 8 . 3651–63 . August 2006 . 16760430 . 1525238 . 10.1091/mbc.E06-02-0112 .
5. Rindler MJ, Xu CF, Gumper I, Cen C, Sonderegger P, Neubert TA . Calsyntenins are secretory granule proteins in anterior pituitary gland and pancreatic islet alpha cells . J. Histochem. Cytochem. . 56 . 4 . 381–8 . April 2008 . 18158283 . 2326105 . 10.1369/jhc.7A7351.2007 .
6. Ludwig A, Blume J, Diep TM, Yuan J, Mateos JM, Leuthäuser K, Steuble M, Streit P, Sonderegger P . Calsyntenins mediate TGN exit of APP in a kinesin-1-dependent manner . Traffic . 10 . 5 . 572–89 . May 2009 . 19192245 . 10.1111/j.1600-0854.2009.00886.x . 205840816 . free .
7. Steuble M, Gerrits B, Ludwig A, Mateos JM, Diep TM, Tagaya M, Stephan A, Schätzle P, Kunz B, Streit P, Sonderegger P . Molecular characterization of a trafficking organelle: dissecting the axonal paths of calsyntenin-1 transport vesicles . Proteomics . 10 . 21 . 3775–88 . November 2010 . 20925061 . 10.1002/pmic.201000384 . 44660376 .
8. Alther TA, Domanitskaya E, Stoeckli ET. Calsyntenin 1-mediated trafficking of axon guidance receptors regulates the switch in axonal responsiveness at a choice point. Development. 2016 Mar 15;143(6):994-1004. | doi: 10.1242/dev.127449. Epub 2016 Feb 2 }
9. 10.1016/j.gendis.2019.09.001. Elevation of gene expression of calcineurin, calmodulin and calsyntenin in oxidative stress induced PC12 cells. 2019. Aravind. P.. Bulbule. Sarojini R.. Hemalatha. N.. Babu. R.L.. Devaraju. K.S.. Genes & Diseases. 8. 1. 87–93. 33569517. 7859428. free.