Rap1-interacting adapter molecule (RIAM) associates with the plasma membrane via a proximity detector
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Author
Wynne, Joseph P.
Wu, Jinhua
Su, Wenjuan
Mor, Adam
Hubbard, Stevan R.
Philips, Mark R.
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https://doi.org/10.1083/jcb.201201157Metadata
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Wynne, Joseph P., Jinhua Wu, Wenjuan Su, Adam Mor, Nikolaos Patsoukis, Vassiliki A. Boussiotis, Stevan R. Hubbard, and Mark R. Philips. 2012. Rap1-interacting adapter molecule (RIAM) associates with the plasma membrane via a proximity detector. The Journal of Cell Biology 199(2): 317-329.Abstract
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)P2) 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)P2.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471229/pdf/Terms of Use
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