Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/81030
Title: Molecular difference between WASP and N-WASP critical for chemotaxis of T-cells towards SDF-1α
Authors: Jain, Neeraj
Thanabalu, Thirumaran
Issue Date: 2015
Source: Jain, N., & Thanabalu, T. (2015). Molecular difference between WASP and N-WASP critical for chemotaxis of T-cells towards SDF-1α. Scientific Reports, 5, 15031-.
Series/Report no.: Scientific Reports
Abstract: Wiskott-Aldrich Syndrome protein (WASP) integrates cell signaling pathways to the actin cytoskeleton, which play a critical role in T-cell activation and migration. 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’s closed conformation and impaired its ability to rescue the chemotactic defect of WASP-deficient (JurkatWKD) T-cells. Expression of N-WASP in JurkatWKD 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 JurkatWKD 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’s failure to compensate for WASP in rescuing chemotaxis could be due to the absence of this I30 region.
URI: https://hdl.handle.net/10356/81030
http://hdl.handle.net/10220/39051
ISSN: 2045-2322
DOI: 10.1038/srep15031
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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