Molecular difference between WASP and N-WASP critical for chemotaxis of T-cells towards SDF-1α
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...
| Main Authors: | , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2015
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| Online Access: | https://hdl.handle.net/10356/81030 http://hdl.handle.net/10220/39051 |
| _version_ | 1811693492038008832 |
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| author | Jain, Neeraj Thanabalu, Thirumaran |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Jain, Neeraj Thanabalu, Thirumaran |
| author_sort | Jain, Neeraj |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T06:52:32Z |
| format | Journal Article |
| id | ntu-10356/81030 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:52:32Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/810302023-02-28T16:59:47Z Molecular difference between WASP and N-WASP critical for chemotaxis of T-cells towards SDF-1α Jain, Neeraj Thanabalu, Thirumaran School of Biological Sciences 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. Published version 2015-12-11T08:03:02Z 2019-12-06T14:19:55Z 2015-12-11T08:03:02Z 2019-12-06T14:19:55Z 2015 Journal Article 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-. 2045-2322 https://hdl.handle.net/10356/81030 http://hdl.handle.net/10220/39051 10.1038/srep15031 26463123 en Scientific Reports 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/ 12 p. application/pdf |
| spellingShingle | Jain, Neeraj Thanabalu, Thirumaran Molecular difference between WASP and N-WASP critical for chemotaxis of T-cells towards SDF-1α |
| title | Molecular difference between WASP and N-WASP critical for chemotaxis of T-cells towards SDF-1α |
| title_full | Molecular difference between WASP and N-WASP critical for chemotaxis of T-cells towards SDF-1α |
| title_fullStr | Molecular difference between WASP and N-WASP critical for chemotaxis of T-cells towards SDF-1α |
| title_full_unstemmed | Molecular difference between WASP and N-WASP critical for chemotaxis of T-cells towards SDF-1α |
| title_short | Molecular difference between WASP and N-WASP critical for chemotaxis of T-cells towards SDF-1α |
| title_sort | molecular difference between wasp and n wasp critical for chemotaxis of t cells towards sdf 1α |
| url | https://hdl.handle.net/10356/81030 http://hdl.handle.net/10220/39051 |
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