Intersectin 1 Explained

Intersectin-1 is a protein that, in humans, is encoded by the ITSN1 gene.^{[1] [2]}

Function

The protein encoded by this gene is a cytoplasmic membrane-associated protein that indirectly coordinates endocytic membrane traffic with the actin assembly machinery. In addition, the encoded protein may regulate the formation of clathrin-coated vesicles and could be involved in synaptic vesicle recycling. This protein has been shown to interact with dynamin, CDC42, SNAP23, SNAP25, SPIN90, EPS15, EPN1, EPN2, and STN2. Multiple transcript variants encoding different isoforms have been found for this gene, but the full-length nature of only two of them have been characterized so far.^[3]

Interactions

ITSN1 has been shown to interact with:

• CDC42,^{[4] [5]}
• SCAMP1^[6]
• SNAP-25,^[7] and
• SOS1.^[8]

References

Further reading

• Keating DJ, Chen C, Pritchard MA . Alzheimer's disease and endocytic dysfunction: clues from the Down syndrome-related proteins, DSCR1 and ITSN1 . Ageing Research Reviews . 5 . 4 . 388–401 . Nov 2006 . 16442855 . 10.1016/j.arr.2005.11.001 . 12867672 .
• Chen H, Antonarakis SE . The SH3D1A gene maps to human chromosome 21q22.1-->q22.2 . Cytogenetics and Cell Genetics . 78 . 3–4 . 213–5 . 1998 . 9465890 . 10.1159/000134659 .
• Sparks AB, Hoffman NG, McConnell SJ, Fowlkes DM, Kay BK . Cloning of ligand targets: systematic isolation of SH3 domain-containing proteins . Nature Biotechnology . 14 . 6 . 741–4 . Jun 1996 . 9630982 . 10.1038/nbt0696-741 . 11166026 .
• Sengar AS, Wang W, Bishay J, Cohen S, Egan SE . The EH and SH3 domain Ese proteins regulate endocytosis by linking to dynamin and Eps15 . The EMBO Journal . 18 . 5 . 1159–71 . Mar 1999 . 10064583 . 1171207 . 10.1093/emboj/18.5.1159 .
• Guipponi M, Scott HS, Hattori M, Ishii K, Sakaki Y, Antonarakis SE . Genomic structure, sequence, and refined mapping of the human intersectin gene (ITSN), which encompasses 250 kb on chromosome 21q22.1-->q22.2 . Cytogenetics and Cell Genetics . 83 . 3–4 . 218–20 . 1999 . 10072581 . 10.1159/000015182 . 27453719 .
• Okamoto M, Schoch S, Südhof TC . EHSH1/intersectin, a protein that contains EH and SH3 domains and binds to dynamin and SNAP-25. A protein connection between exocytosis and endocytosis? . The Journal of Biological Chemistry . 274 . 26 . 18446–54 . Jun 1999 . 10373452 . 10.1074/jbc.274.26.18446 . free .
• Pucharcós C, Fuentes JJ, Casas C, de la Luna S, Alcántara S, Arbonés ML, Soriano E, Estivill X, Pritchard M . Alu-splice cloning of human Intersectin (ITSN), a putative multivalent binding protein expressed in proliferating and differentiating neurons and overexpressed in Down syndrome . European Journal of Human Genetics . 7 . 6 . 704–12 . Sep 1999 . 10482960 . 10.1038/sj.ejhg.5200356 . free .
• Tong XK, Hussain NK, de Heuvel E, Kurakin A, Abi-Jaoude E, Quinn CC, Olson MF, Marais R, Baranes D, Kay BK, McPherson PS . The endocytic protein intersectin is a major binding partner for the Ras exchange factor mSos1 in rat brain . The EMBO Journal . 19 . 6 . 1263–71 . Mar 2000 . 10716926 . 305667 . 10.1093/emboj/19.6.1263 .
• Fernández-Chacón R, Achiriloaie M, Janz R, Albanesi JP, Südhof TC . SCAMP1 function in endocytosis . The Journal of Biological Chemistry . 275 . 17 . 12752–6 . Apr 2000 . 10777571 . 10.1074/jbc.275.17.12752 . free .
• Pucharcos C, Estivill X, de la Luna S . Intersectin 2, a new multimodular protein involved in clathrin-mediated endocytosis . FEBS Letters . 478 . 1–2 . 43–51 . Jul 2000 . 10922467 . 10.1016/S0014-5793(00)01793-2 . 24683452 .
• Martina JA, Bonangelino CJ, Aguilar RC, Bonifacino JS . Stonin 2: an adaptor-like protein that interacts with components of the endocytic machinery . The Journal of Cell Biology . 153 . 5 . 1111–20 . May 2001 . 11381094 . 2174325 . 10.1083/jcb.153.5.1111 .
• Hussain NK, Jenna S, Glogauer M, Quinn CC, Wasiak S, Guipponi M, Antonarakis SE, Kay BK, Stossel TP, Lamarche-Vane N, McPherson PS . Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP . Nature Cell Biology . 3 . 10 . 927–32 . Oct 2001 . 11584276 . 10.1038/ncb1001-927 . 22914248 .
• Pucharcos C, Casas C, Nadal M, Estivill X, de la Luna S . The human intersectin genes and their spliced variants are differentially expressed . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1521 . 1–3 . 1–11 . Oct 2001 . 11690630 . 10.1016/s0167-4781(01)00276-7 .
• Jenna S, Hussain NK, Danek EI, Triki I, Wasiak S, McPherson PS, Lamarche-Vane N . The activity of the GTPase-activating protein CdGAP is regulated by the endocytic protein intersectin . The Journal of Biological Chemistry . 277 . 8 . 6366–73 . Feb 2002 . 11744688 . 10.1074/jbc.M105516200 . free .
• Snyder JT, Worthylake DK, Rossman KL, Betts L, Pruitt WM, Siderovski DP, Der CJ, Sondek J . Structural basis for the selective activation of Rho GTPases by Dbl exchange factors . Nature Structural Biology . 9 . 6 . 468–75 . Jun 2002 . 12006984 . 10.1038/nsb796 . 13161854 .
• Irie F, Yamaguchi Y . EphB receptors regulate dendritic spine development via intersectin, Cdc42 and N-WASP . Nature Neuroscience . 5 . 11 . 1117–8 . Nov 2002 . 12389031 . 10.1038/nn964 . 130279 .

Notes and References

1. Guipponi M, Scott HS, Chen H, Schebesta A, Rossier C, Antonarakis SE . Two isoforms of a human intersectin (ITSN) protein are produced by brain-specific alternative splicing in a stop codon . Genomics . 53 . 3 . 369–76 . Nov 1998 . 9799604 . 10.1006/geno.1998.5521 .
2. Yamabhai M, Hoffman NG, Hardison NL, McPherson PS, Castagnoli L, Cesareni G, Kay BK . Intersectin, a novel adaptor protein with two Eps15 homology and five Src homology 3 domains . The Journal of Biological Chemistry . 273 . 47 . 31401–7 . Nov 1998 . 9813051 . 10.1074/jbc.273.47.31401 . free .
3. Web site: Entrez Gene: ITSN1 intersectin 1 (SH3 domain protein).
4. Hussain NK, Jenna S, Glogauer M, Quinn CC, Wasiak S, Guipponi M, Antonarakis SE, Kay BK, Stossel TP, Lamarche-Vane N, McPherson PS . Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP . Nature Cell Biology . 3 . 10 . 927–32 . Oct 2001 . 11584276 . 10.1038/ncb1001-927 . 22914248 .
5. Snyder JT, Worthylake DK, Rossman KL, Betts L, Pruitt WM, Siderovski DP, Der CJ, Sondek J . Structural basis for the selective activation of Rho GTPases by Dbl exchange factors . Nature Structural Biology . 9 . 6 . 468–75 . Jun 2002 . 12006984 . 10.1038/nsb796 . 13161854 .
6. Fernández-Chacón R, Achiriloaie M, Janz R, Albanesi JP, Südhof TC . SCAMP1 function in endocytosis . The Journal of Biological Chemistry . 275 . 17 . 12752–6 . Apr 2000 . 10777571 . 10.1074/jbc.275.17.12752. free .
7. Okamoto M, Schoch S, Südhof TC . EHSH1/intersectin, a protein that contains EH and SH3 domains and binds to dynamin and SNAP-25. A protein connection between exocytosis and endocytosis? . The Journal of Biological Chemistry . 274 . 26 . 18446–54 . Jun 1999 . 10373452 . 10.1074/jbc.274.26.18446. free .
8. Tong XK, Hussain NK, de Heuvel E, Kurakin A, Abi-Jaoude E, Quinn CC, Olson MF, Marais R, Baranes D, Kay BK, McPherson PS . The endocytic protein intersectin is a major binding partner for the Ras exchange factor mSos1 in rat brain . The EMBO Journal . 19 . 6 . 1263–71 . Mar 2000 . 10716926 . 305667 . 10.1093/emboj/19.6.1263 .