title: Molecular difference between WASP and N-WASP critical for chemotaxis of T-cells towards SDF-1α.
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 (Jurkat(WKD)) T-cells. Expression of N-WASP in Jurkat(WKD) 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(WKD) 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.
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Republic of Singapore.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Jain
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Republic of Singapore.
authors.forename: Thirumaran
authors.initials: T
authors.lastname: Thanabalu
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D054377:Chemokine CXCL12 / Q000737:chemistry / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000737:chemistry / Q000378:metabolism*; D051316:Wiskott-Aldrich Syndrome Protein / Q000737:chemistry* / Q000378:metabolism*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D054377:Chemokine CXCL12; D051316:Wiskott-Aldrich Syndrome Protein; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal