| First Author | Kamioka Y | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 6 | Pages | 112580 |
| PubMed ID | 37267105 | Mgi Jnum | J:338516 |
| Mgi Id | MGI:7491417 | Doi | 10.1016/j.celrep.2023.112580 |
| Citation | Kamioka Y, et al. (2023) Distinct bidirectional regulation of LFA1 and alpha4beta7 by Rap1 and integrin adaptors in T cells under shear flow. Cell Rep 42(6):112580 |
| abstractText | 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 alpha4beta7 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 talin1, but not kindlin-3, resulting in increased capture and slowing. In contrast, none of them were required for tether/rolling by alpha4beta7 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 alpha4beta7, activated Rap1 severely suppressed adhesion on MAdCAM1 under shear flow, indicating the critical importance of a sequential outside-in/inside-out signaling for alpha4beta7. |
