Reference - Detail
| RRC ID | 76721 |
|---|---|
| Author | Kamioka Y, Ueda Y, Kondo N, Tokuhiro K, Ikeda Y, Bergmeier W, Kinashi T. |
| Title | Distinct bidirectional regulation of LFA1 and α4β7 by Rap1 and integrin adaptors in T cells under shear flow. |
| Journal | Cell Rep |
| Abstract |
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 α4β7 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 α4β7 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 α4β7, activated Rap1 severely suppressed adhesion on MAdCAM1 under shear flow, indicating the critical importance of a sequential outside-in/inside-out signaling for α4β7. |
| Volume | 42(6) |
| Pages | 112580 |
| Published | 2023-6-1 |
| DOI | 10.1016/j.celrep.2023.112580 |
| PII | S2211-1247(23)00591-0 |
| PMID | 37267105 |
| IF | 8.109 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 6 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| DNA material | pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |