CLINT1 explained

Clathrin interactor 1 (CLINT1), also known as EPSIN4, is a protein which in humans is encoded by the CLINT1 gene.^{[1] [2] [3]}

Function

The CLINT1 protein binds to the terminal domain of the clathrin heavy chain and stimulates clathrin cage vesicle assembly. Clathrin coated vesicles enable neurotransmitter receptors and other proteins to be endocytosed or taken up across neuronal membranes and across the membranes of other types of cells. This enables a turnover of neuroreceptors or other proteins to be maintained and thus the numbers of receptors can be fine tuned.^[2]

Clinical significance

The CLINT1 gene has been shown to be involved in the genetic aetiology of schizophrenia in four studies ^{[4] [5] [6] [7] [8]} It is known that the antipsychotic drugs chlorpromazine and clozapine stabilise clathrin coated vesicles^{[9] [10]} and this may be one reason why antipsychotic drugs are effective in treating delusions, auditory hallucinations and many of the other symptoms of schizophrenia.

Interactions

CLINT1 has been shown to interact with GGA2.

Further reading

• Nagase T, Seki N, Ishikawa K . Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1. . DNA Res. . 3 . 1 . 17–24 . 1996 . 8724849 . 10.1093/dnares/3.1.17 . etal. free .
• Hoja MR, Wahlestedt C, Höög C . A visual intracellular classification strategy for uncharacterized human proteins. . Exp. Cell Res. . 259 . 1 . 239–46 . 2000 . 10942595 . 10.1006/excr.2000.4948 .
• Wasiak S, Legendre-Guillemin V, Puertollano R . Enthoprotin: a novel clathrin-associated protein identified through subcellular proteomics. . J. Cell Biol. . 158 . 5 . 855–62 . 2002 . 12213833 . 10.1083/jcb.200205078 . 2173151 . etal.
• Kalthoff C, Groos S, Kohl R . Clint: a novel clathrin-binding ENTH-domain protein at the Golgi. . Mol. Biol. Cell . 13 . 11 . 4060–73 . 2003 . 12429846 . 10.1091/mbc.E02-03-0171 . 133614 . etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Mills IG, Praefcke GJ, Vallis Y . EpsinR: an AP1/clathrin interacting protein involved in vesicle trafficking. . J. Cell Biol. . 160 . 2 . 213–22 . 2003 . 12538641 . 10.1083/jcb.200208023 . 2172650 . etal.
• Hirst J, Motley A, Harasaki K . EpsinR: an ENTH domain-containing protein that interacts with AP-1. . Mol. Biol. Cell . 14 . 2 . 625–41 . 2003 . 12589059 . 10.1091/mbc.E02-09-0552 . 149997 . etal.
• Wasiak S, Denisov AY, Han Z . Characterization of a gamma-adaptin ear-binding motif in enthoprotin. . FEBS Lett. . 555 . 3 . 437–42 . 2004 . 14675752 . 10.1016/S0014-5793(03)01299-7 . 84390010 . etal. free .
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .
• Saint-Pol A, Yélamos B, Amessou M . Clathrin adaptor epsinR is required for retrograde sorting on early endosomal membranes. . Dev. Cell . 6 . 4 . 525–38 . 2004 . 15068792 . 10.1016/S1534-5807(04)00100-5 . etal. free .
• Jin J, Smith FD, Stark C . Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization. . Curr. Biol. . 14 . 16 . 1436–50 . 2004 . 15324660 . 10.1016/j.cub.2004.07.051 . 2371325 . etal. free . 2004CBio...14.1436J .
• Hirst J, Miller SE, Taylor MJ . EpsinR is an adaptor for the SNARE protein Vti1b. . Mol. Biol. Cell . 15 . 12 . 5593–602 . 2005 . 15371541 . 10.1091/mbc.E04-06-0468 . 532037 . etal.
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Pimm J, McQuillin A, Thirumalai S . 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 . 2005 . 15793701 . 10.1086/430095 . 1199380 . etal.
• Rual JF, Venkatesan K, Hao T . Towards a proteome-scale map of the human protein-protein interaction network. . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 . etal.
• Tang RQ, Zhao XZ, Shi YY . Family-based association study of Epsin 4 and Schizophrenia. . Mol. Psychiatry . 11 . 4 . 395–9 . 2006 . 16402136 . 10.1038/sj.mp.4001780 . etal. free .
• Olsen JV, Blagoev B, Gnad F . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. . Cell . 127 . 3 . 635–48 . 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . 7827573 . etal. free .

Notes and References

1. Web site: Entrez Gene: CLINT1 clathrin interactor 1.
2. Wasiak S, Legendre-Guillemin V, Puertollano R, Blondeau F, Girard M, de Heuvel E, Boismenu D, Bell AW, Bonifacino JS, McPherson PS . Enthoprotin: a novel clathrin-associated protein identified through subcellular proteomics . J. Cell Biol. . 158 . 5 . 855–62 . September 2002 . 12213833 . 2173151 . 10.1083/jcb.200205078 .
3. Kalthoff C, Groos S, Kohl R, Mahrhold S, Ungewickell EJ . Clint: a novel clathrin-binding ENTH-domain protein at the Golgi . Mol. Biol. Cell . 13 . 11 . 4060–73 . November 2002 . 12429846 . 133614 . 10.1091/mbc.E02-03-0171 .
4. Pimm J, McQuillin A, Thirumalai S, Lawrence J, Quested D, Bass N, Lamb G, Moorey H, Datta SR, Kalsi G, Badacsonyi A, Kelly K, Morgan J, Punukollu B, Curtis D, Gurling H . 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 . May 2005 . 15793701 . 1199380 . 10.1086/430095 .
5. Gurling H, Pimm J, McQuillin A . 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 . January 2007 . 17070672 . 10.1016/j.schres.2006.08.024 . 43407088 .
6. Tang RQ, Zhao XZ, Shi YY, Tang W, Gu NF, Feng GY, Xing YL, Zhu SM, Sang H, Liang PJ, He L . Family-based association study of Epsin 4 and Schizophrenia . Mol. Psychiatry . 11 . 4 . 395–9 . April 2006 . 16402136 . 10.1038/sj.mp.4001780 . free .
7. Liou YJ, Lai IC, Wang YC, Bai YM, Lin CC, Lin CY, Chen TT, Chen JY . Genetic analysis of the human ENTH (Epsin 4) gene and schizophrenia . Schizophr. Res. . 84 . 2–3 . 236–43 . June 2006 . 16616458 . 10.1016/j.schres.2006.02.021 . 23934037 .
8. Escamilla M, Lee BD, Ontiveros A, Raventos H, Nicolini H, Mendoza R, Jerez A, Munoz R, Medina R, Figueroa A, Walss-Bass C, Armas R, Contreras S, Ramirez ME, Dassori A . The epsin 4 gene is associated with psychotic disorders in families of Latin American origin . Schizophr. Res. . 106 . 2–3 . 253–7 . December 2008 . 18929466 . 10.1016/j.schres.2008.09.005 . 24978042 .
9. Phonphok Y, Rosenthal KS . Stabilization of clathrin coated vesicles by amantadine, tromantadine and other hydrophobic amines . FEBS Lett. . 281 . 1–2 . 188–90 . April 1991 . 1901801 . 10.1016/0014-5793(91)80390-O . 8197032 . free .
10. Claing A, Perry SJ, Achiriloaie M, Walker JK, Albanesi JP, Lefkowitz RJ, Premont RT. Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity . Proc. Natl. Acad. Sci. U.S.A. . 97 . 3 . 1119–24 . February 2000 . 10655494 . 15541 . 10.1073/pnas.97.3.1119. 2000PNAS...97.1119C . free .