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The small GTPase, Rap1, mediates CD31-induced integrin adhesion.
K A Reedquist1, E Ross, E A Koop
1Laboratory for Physiological Chemistry, Centre for Biomedical Genetics, Utrecht University Medical Center, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.
The Journal of Cell Biology
|March 22, 2000
Summary
CD31 signaling activates the Rap1 GTPase, crucial for T cell adhesion to ICAM and VCAM via integrins. This reveals Rap1
Area of Science:
- Immunology
- Cell Biology
- Molecular Signaling
Background:
- Leukocyte adhesion is vital for immune responses and tightly regulated.
- Integration of signals from adhesion receptors (like CD31) and mitogenic stimuli is poorly understood.
- CD31 acts as an adhesion amplifier, influencing leukocyte function.
Purpose of the Study:
- To elucidate the signaling pathways by which CD31 regulates T cell adhesion.
- To identify key molecular mediators involved in CD31-induced integrin activation.
- To understand how CD31 signaling integrates with other cellular pathways.
Main Methods:
- Investigated CD31's cytoplasmic tail function in T cell adhesion.
- Utilized mutant forms of small GTPases (Rap1, Ras, R-Ras, Rap2) and related signaling molecules (C3G, RapGAP).
- Assessed T cell adhesion to ICAM and VCAM under various signaling conditions.
Main Results:
- CD31 signaling propagates through its cytoplasmic tail to activate beta1 (VLA-4) and beta2 (LFA-1) integrins.
- The small GTPase Rap1 was identified as a critical mediator of CD31-induced T cell adhesion.
- CD31 selectively activated Rap1, not Ras, R-Ras, or Rap2; manipulation of Rap1 signaling components altered T cell adhesion.
Conclusions:
- Rap1 plays a novel and essential role in regulating ligand-induced cell adhesion.
- CD31-mediated T cell adhesion is dependent on Rap1 activation.
- Rap1 may coordinate adhesion signals during leukocyte migration and extravasation, and potentially mediate transformation reversion.