Journal
CELL REPORTS
Volume 42, Issue 6, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2023.112580
Keywords
-
Categories
Ask authors/readers for more resources
Bidirectional control of integrin activation plays crucial roles in cell adhesive behaviors. In this study, distinct bidirectional regulation of LFA1 and Or4137 in primary T cells was observed. Outside-in signaling from ICAM1-interacting LFA1 activated Rap1 GTPase and talin1, leading to increased capture and slowing. However, activated Rap1 severely suppressed adhesion of Or4137 on MAdCAM1 under shear flow.
Bidirectional control of integrin activation plays crucial roles in cell adhesive behaviors, but how integrins are specifically regulated by inside-out and outside-in signaling has not been fully understood. Here, we report distinct bidirectional regulation of major lymphocyte homing receptors LFA1 and or4137 in primary T cells. A small increase of Rap1 activation in L-selectin-mediated tether/rolling was boosted by the outside-in signaling from ICAM1-interacting LFA1 through subsecond, simultaneous activation of Rap1 GTPase and ta-lin1, but not kindlin-3, resulting in increased capture and slowing. In contrast, none of them were required for tether/rolling by or4137 on MAdCAM1. High Rap1 activation with chemokines or the loss of Rap1-inactivating proteins Rasa3 and Sipa1 increased talin1/kindlin-3-dependent arrest with high-affinity binding of LFA1 to membrane-anchored ICAM1. However, despite increased affinity of or4137, activated Rap1 severely suppressed adhesion on MAdCAM1 under shear flow, indicating the critical importance of a sequential outside-in/inside-out signaling for or4137.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available