Calsyntenin

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]

Calsyntenin
Identifiers
SymbolCLSTN
InterProIPR026914
Membranome241

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]

References
  1. Vogt L, Schrimpf SP, Meskenaite V, Frischknecht R, Kinter J, Leone DP, Ziegler U, Sonderegger P (January 2001). "Calsyntenin-1, a proteolytically processed postsynaptic membrane protein with a cytoplasmic calcium-binding domain". Mol. Cell. Neurosci. 17 (1): 151–66. doi:10.1006/mcne.2000.0937. PMID 11161476.
  2. Hintsch G, Zurlinden A, Meskenaite V, Steuble M, Fink-Widmer K, Kinter J, Sonderegger P (November 2002). "The calsyntenins--a family of postsynaptic membrane proteins with distinct neuronal expression patterns". Mol. Cell. Neurosci. 21 (3): 393–409. doi:10.1006/mcne.2002.1181. PMID 12498782.
  3. Ikeda DD, Duan Y, Matsuki M, Kunitomo H, Hutter H, Hedgecock EM, Iino Y (April 2008). "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. doi:10.1073/pnas.0711894105. PMC 2278220. PMID 18381821.
  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 (August 2006). "Calsyntenin-1 docks vesicular cargo to kinesin-1" (PDF). Mol. Biol. Cell. 17 (8): 3651–63. doi:10.1091/mbc.E06-02-0112. PMC 1525238. PMID 16760430.
  5. Rindler MJ, Xu CF, Gumper I, Cen C, Sonderegger P, Neubert TA (April 2008). "Calsyntenins are secretory granule proteins in anterior pituitary gland and pancreatic islet alpha cells". J. Histochem. Cytochem. 56 (4): 381–8. doi:10.1369/jhc.7A7351.2007. PMC 2326105. PMID 18158283.
  6. Ludwig A, Blume J, Diep TM, Yuan J, Mateos JM, Leuthäuser K, Steuble M, Streit P, Sonderegger P (May 2009). "Calsyntenins mediate TGN exit of APP in a kinesin-1-dependent manner". Traffic. 10 (5): 572–89. doi:10.1111/j.1600-0854.2009.00886.x. PMID 19192245.
  7. Steuble M, Gerrits B, Ludwig A, Mateos JM, Diep TM, Tagaya M, Stephan A, Schätzle P, Kunz B, Streit P, Sonderegger P (November 2010). "Molecular characterization of a trafficking organelle: dissecting the axonal paths of calsyntenin-1 transport vesicles". Proteomics. 10 (21): 3775–88. doi:10.1002/pmic.201000384. PMID 20925061.
  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. Aravind, P.; Bulbule, Sarojini R.; Hemalatha, N.; Babu, R.L.; Devaraju, K.S. (2019). "Elevation of gene expression of calcineurin, calmodulin and calsyntenin in oxidative stress induced PC12 cells". Genes & Diseases. doi:10.1016/j.gendis.2019.09.001.
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