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Rap1-interacting adapter molecule (RIAM) associates with the plasma membrane via a proximity detector
Adaptive immunity depends on lymphocyte adhesion that is mediated by the integrin lymphocyte functional antigen 1 (LFA-1). The small guanosine triphosphatase Rap1 regulates LFA-1 adhesiveness through one of its effectors, Rap1-interacting adapter molecule (RIAM). We show that RIAM was recruited to t...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471229/ https://www.ncbi.nlm.nih.gov/pubmed/23045549 http://dx.doi.org/10.1083/jcb.201201157 |
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author | Wynne, Joseph P. Wu, Jinhua Su, Wenjuan Mor, Adam Patsoukis, Nikolaos Boussiotis, Vassiliki A. Hubbard, Stevan R. Philips, Mark R. |
author_facet | Wynne, Joseph P. Wu, Jinhua Su, Wenjuan Mor, Adam Patsoukis, Nikolaos Boussiotis, Vassiliki A. Hubbard, Stevan R. Philips, Mark R. |
author_sort | Wynne, Joseph P. |
collection | PubMed |
description | Adaptive immunity depends on lymphocyte adhesion that is mediated by the integrin lymphocyte functional antigen 1 (LFA-1). The small guanosine triphosphatase Rap1 regulates LFA-1 adhesiveness through one of its effectors, Rap1-interacting adapter molecule (RIAM). We show that RIAM was recruited to the lymphocyte plasma membrane (PM) through its Ras association (RA) and pleckstrin homology (PH) domains, both of which were required for lymphocyte adhesion. The N terminus of RIAM inhibited membrane translocation. In vitro, the RA domain bound both Rap1 and H-Ras with equal but relatively low affinity, whereas in vivo only Rap1 was required for PM association. The PH domain bound phosphoinositol 4,5-bisphosphate (PI(4,5)P(2)) and was responsible for the spatial distribution of RIAM only at the PM of activated T cells. We determined the crystal structure of the RA and PH domains and found that, despite an intervening linker of 50 aa, the two domains were integrated into a single structural unit, which was critical for proper localization to the PM. Thus, the RA-PH domains of RIAM function as a proximity detector for activated Rap1 and PI(4,5)P(2). |
format | Online Article Text |
id | pubmed-3471229 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-34712292013-04-15 Rap1-interacting adapter molecule (RIAM) associates with the plasma membrane via a proximity detector Wynne, Joseph P. Wu, Jinhua Su, Wenjuan Mor, Adam Patsoukis, Nikolaos Boussiotis, Vassiliki A. Hubbard, Stevan R. Philips, Mark R. J Cell Biol Research Articles Adaptive immunity depends on lymphocyte adhesion that is mediated by the integrin lymphocyte functional antigen 1 (LFA-1). The small guanosine triphosphatase Rap1 regulates LFA-1 adhesiveness through one of its effectors, Rap1-interacting adapter molecule (RIAM). We show that RIAM was recruited to the lymphocyte plasma membrane (PM) through its Ras association (RA) and pleckstrin homology (PH) domains, both of which were required for lymphocyte adhesion. The N terminus of RIAM inhibited membrane translocation. In vitro, the RA domain bound both Rap1 and H-Ras with equal but relatively low affinity, whereas in vivo only Rap1 was required for PM association. The PH domain bound phosphoinositol 4,5-bisphosphate (PI(4,5)P(2)) and was responsible for the spatial distribution of RIAM only at the PM of activated T cells. We determined the crystal structure of the RA and PH domains and found that, despite an intervening linker of 50 aa, the two domains were integrated into a single structural unit, which was critical for proper localization to the PM. Thus, the RA-PH domains of RIAM function as a proximity detector for activated Rap1 and PI(4,5)P(2). The Rockefeller University Press 2012-10-15 /pmc/articles/PMC3471229/ /pubmed/23045549 http://dx.doi.org/10.1083/jcb.201201157 Text en © 2012 Wynne et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Wynne, Joseph P. Wu, Jinhua Su, Wenjuan Mor, Adam Patsoukis, Nikolaos Boussiotis, Vassiliki A. Hubbard, Stevan R. Philips, Mark R. Rap1-interacting adapter molecule (RIAM) associates with the plasma membrane via a proximity detector |
title | Rap1-interacting adapter molecule (RIAM) associates with the plasma membrane via a proximity detector |
title_full | Rap1-interacting adapter molecule (RIAM) associates with the plasma membrane via a proximity detector |
title_fullStr | Rap1-interacting adapter molecule (RIAM) associates with the plasma membrane via a proximity detector |
title_full_unstemmed | Rap1-interacting adapter molecule (RIAM) associates with the plasma membrane via a proximity detector |
title_short | Rap1-interacting adapter molecule (RIAM) associates with the plasma membrane via a proximity detector |
title_sort | rap1-interacting adapter molecule (riam) associates with the plasma membrane via a proximity detector |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471229/ https://www.ncbi.nlm.nih.gov/pubmed/23045549 http://dx.doi.org/10.1083/jcb.201201157 |
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