Epsin

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Epsins are a family of membrane proteins that are important in creating membrane curvature. Epsins contribute to membrane deformations like endocytosis, and block vesicle formation during mitosis.

Epsins have many different domains to interact with various proteins related to endocytosis. At its N-terminus is an ENTH domain that binds phosphatidylinositol (4,5)-bisphosphate, meaning that it binds a lipid of biological membranes. It has also been postulated that this is a site for cargo-binding. In the middle of the epsin sequence are two UIMs (ubiquitin-interacting motifs). The C-terminus contains multiple binding sites, for example for clathrin and AP2 adaptors. As such, epsins are able to bind to membranes with specific cargo and connect them with the endocytosis machinery, so one may understand epsins as something like Swiss army knives for endocytosis. They may be the major membrane curvature-driving proteins in many clathrin-coated vesicle budding events.

Epsin 4, which encodes the protein enthoprotin, now known as clathrin interactor 1 (CLINT1), has been shown to be involved in the genetic susceptibility to schizophrenia in four independent studies.[1][2][3][4][5] A genetic abnormality in CLINT1 is assumed to change the way internalisation of neurotransmitter receptors occurs in the brains of people with schizophrenia.

The epsin homologue of C.elegans is EPN-1. EPN-1 conserves the UIM, ENTH domain, and clathrin-binding motif.

References[edit]

  1. ^ Pimm J, McQuillin A, Thirumalai S, et al. (May 2005). "The Epsin 4 gene on chromosome 5q, which encodes the clathrin-associated protein enthoprotin, is involved in the genetic susceptibility to schizophrenia". Am. J. Hum. Genet. 76 (5): 902–7. doi:10.1086/430095. PMC 1199380. PMID 15793701. 
  2. ^ Tang RQ, Zhao XZ, Shi YY, et al. (April 2006). "Family-based association study of Epsin 4 and Schizophrenia". Mol. Psychiatry 11 (4): 395–9. doi:10.1038/sj.mp.4001780. PMID 16402136. 
  3. ^ Liou YJ, Lai IC, Wang YC, et al. (June 2006). "Genetic analysis of the human ENTH (Epsin 4) gene and schizophrenia". Schizophr. Res. 84 (2-3): 236–43. doi:10.1016/j.schres.2006.02.021. PMID 16616458. 
  4. ^ Gurling H, Pimm J, McQuillin A (January 2007). "Replication of genetic association studies between markers at the Epsin 4 gene locus and schizophrenia in two Han Chinese samples". Schizophr. Res. 89 (1-3): 357–9. doi:10.1016/j.schres.2006.08.024. PMID 17070672. 
  5. ^ Escamilla M, Lee BD, Ontiveros A, et al. (December 2008). "The epsin 4 gene is associated with psychotic disorders in families of Latin American origin". Schizophr. Res. 106 (2-3): 253–7. doi:10.1016/j.schres.2008.09.005. PMID 18929466. 

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