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Hematopoietic cells express both WASP and neural-WASP (N-WASP) which share similar domain structure, yet WASP deficiency causes Wiskott-Aldrich syndrome, suggesting that N-WASP present in the cells is not able to carry out all the functions of WASP. We have identified a unique internal thirty amino acid region (I30) in WASP, which regulates its function in chemotaxis of Jurkat T-cells. Deletion of the I30 region altered the WASP\u2019s closed conformation and impaired its ability to rescue the chemotactic defect of WASP-deficient (Jurkat<jats:sup>WKD<\/jats:sup>) T-cells. Expression of N-WASP in Jurkat<jats:sup>WKD<\/jats:sup> T-cells using WASP promoter restored the migration velocity without correcting the chemotactic defect. However, insertion of I30 region in N-WASP (N-WASP-I30) enabled N-WASP to rescue the chemotactic defect of Jurkat<jats:sup>WKD<\/jats:sup> T-cells. N-WASP-I30-EGFP displayed a punctate localization in contrast to the predominant nuclear localization of N-WASP-EGFP. Thus, our study has demonstrated that the I30 region of WASP is critical for localization and chemotaxis. This suggests that N-WASP\u2019s failure to compensate for WASP in rescuing chemotaxis could be due to the absence of this I30 region.<\/jats:p>","DOI":"10.1038\/srep15031","type":"journal-article","created":{"date-parts":[[2015,10,14]],"date-time":"2015-10-14T10:36:04Z","timestamp":1444818964000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Molecular difference between WASP and N-WASP critical for chemotaxis of T-cells towards SDF-1\u03b1"],"prefix":"10.1038","volume":"5","author":[{"given":"Neeraj","family":"Jain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thirumaran","family":"Thanabalu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,10,14]]},"reference":[{"key":"BFsrep15031_CR1","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/nrm2069","volume":"8","author":"T Takenawa","year":"2007","unstructured":"Takenawa, T. & Suetsugu, S. 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