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Function
Intersectin (ITSN) is an endocytic multidomain scaffold protein in neurons and is important regulator of synaptic vescicles replenishment at hippocampal synapses. The replenishment is needed in order to sustain neurotransmission during periods of elevated activity. ITSN interacts with synapsin I through its SH3 domains[1]. Alternative splicing of ITSN generates a short isoform with 2 EH (Eps15 homology) domains and 5 SH3 domains and a long isoform with additional DH, PH and C2 domains[2],[3].
ITSN 2 is also involved in clathrin-mediated endocytosis and is very similar to ITSN 1.
ITSN-1 has two isoforms as a result of differential splicing:
- ITSN-1 short form is 140kD and expressed in all tissues
- ITSN-1 long form is 200kD and expressed in neutrons, eye, heart, blood cells and kidney[4].
- ITSN-2 short form contains 2 EH domains, a coiled-coil domain and 5 SH3 domains
- ITSN-2 long formcontains an extra carboxylate domain[5].
Relevance
ITSN 1 is expressed in neuroblastoma tumors and tumor cell lines and is necessary for their tumorigenic properties[6].
ITSN 2 might be a potential biomarker for discrimination of severe acute pancreatitis to improve the prognosis of patients[7]. Overexpression of ITSN 1 is implicated for human neurodegenerative diseases such as Down's syndrome and Alzheimer's disease[8].
Structural highlights
The 3D structure of the complex between the SH3 domains of ITSN 1 and FCHSD2 shows extensive contact surface composed mainly of hydrophobic interactions[9].
- ↑ . Correction for Gerth et al., Intersectin associates with synapsin and regulates its nanoscale localization and function. Proc Natl Acad Sci U S A. 2017 Dec 19;114(51):E11060. doi:, 10.1073/pnas.1720226115. Epub 2017 Dec 11. PMID:29229830 doi:https://dx.doi.org/10.1073/pnas.1720226115
- ↑ Ma N, Niu RF, Ma YJ. Intersectin 1: a molecular linker in the central nervous system. Neurosci Bull. 2008 Dec;24(6):401-5. doi: 10.1007/s12264-008-0715-0. PMID:19037327 doi:https://dx.doi.org/10.1007/s12264-008-0715-0
- ↑ Pucharcos C, Estivill X, de la Luna S. Intersectin 2, a new multimodular protein involved in clathrin-mediated endocytosis. FEBS Lett. 2000 Jul 28;478(1-2):43-51. doi: 10.1016/s0014-5793(00)01793-2. PMID:10922467 doi:https://dx.doi.org/10.1016/s0014-5793(00)01793-2
- ↑ Malakooti N, Pritchard MA, Chen F, Yu Y, Sgambelloni C, Adlard PA, Finkelstein DI. The Long Isoform of Intersectin-1 Has a Role in Learning and Memory. Front Behav Neurosci. 2020 Feb 25;14:24. PMID:32161523 doi:10.3389/fnbeh.2020.00024
- ↑ Pucharcos C, Estivill X, de la Luna S. Intersectin 2, a new multimodular protein involved in clathrin-mediated endocytosis. FEBS Lett. 2000 Jul 28;478(1-2):43-51. doi: 10.1016/s0014-5793(00)01793-2. PMID:10922467 doi:https://dx.doi.org/10.1016/s0014-5793(00)01793-2
- ↑ Russo A, O'Bryan JP. Intersectin 1 is required for neuroblastoma tumorigenesis. Oncogene. 2012 Nov 15;31(46):4828-34. doi: 10.1038/onc.2011.643. Epub 2012 Jan, 23. PMID:22266851 doi:https://dx.doi.org/10.1038/onc.2011.643
- ↑ Li J, Bu X, Chen X, Xiong P, Chen Z, Yu L. Predictive value of long non-coding RNA intersectin 1-2 for occurrence and in-hospital mortality of severe acute pancreatitis. J Clin Lab Anal. 2019 Dec 27:e23170. doi: 10.1002/jcla.23170. PMID:31880027 doi:https://dx.doi.org/10.1002/jcla.23170
- ↑ Hunter MP, Nelson M, Kurzer M, Wang X, Kryscio RJ, Head E, Pinna G, O'Bryan JP. Intersectin 1 contributes to phenotypes in vivo: implications for Down's syndrome. Neuroreport. 2011 Oct 26;22(15):767-72. doi: 10.1097/WNR.0b013e32834ae348. PMID:21876463 doi:https://dx.doi.org/10.1097/WNR.0b013e32834ae348
- ↑ Almeida-Souza L, Frank RAW, Garcia-Nafria J, Colussi A, Gunawardana N, Johnson CM, Yu M, Howard G, Andrews B, Vallis Y, McMahon HT. A Flat BAR Protein Promotes Actin Polymerization at the Base of Clathrin-Coated Pits. Cell. 2018 Jun 4. pii: S0092-8674(18)30597-X. doi: 10.1016/j.cell.2018.05.020. PMID:29887380 doi:https://dx.doi.org/10.1016/j.cell.2018.05.020
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