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Membranes as messengers in T cell adhesion signaling

Abstract

Talin and RapL are components of molecular pathways that regulate the avidity of the integrin lymphocyte function–associated antigen 1 (LFA-1) for its ligand, intercellular adhesion molecule 1. In this review, we discuss recent advances in our understanding of LFA-1 affinity regulation and signaling and discuss a scenario for how Talin and Rap1 might act in synergy to achieve regulation of LFA-1 that is tailored to the specific functional requirements of different situations. Speedy delivery of signals may be crucial, and membrane trafficking from endosomes and the Golgi apparatus seem to be essential in delivering the messages from spatially segregated surface receptors.

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Figure 1: Structural model of LFA-1.
Figure 2: Combinatorial interactions of Talin, Rap1-RapL and ICAM-1 to regulate integrin affinity and mobility.
Figure 3: Model for inside-out signaling and function of recycling endosomes.

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Acknowledgements

The authors acknowledge the contributions of our respective laboratories. Supported by the National Institutes of Health (AI44931 and AI43542 to M.L.D. and GM55279 to M.R.P.), Irene Diamond Foundation (M.L.D.), and Burroughs Wellcome Fund (M.R.P.).

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Dustin, M., Bivona, T. & Philips, M. Membranes as messengers in T cell adhesion signaling. Nat Immunol 5, 363–372 (2004). https://doi.org/10.1038/ni1057

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