| RRC ID |
76721
|
| 著者 |
Kamioka Y, Ueda Y, Kondo N, Tokuhiro K, Ikeda Y, Bergmeier W, Kinashi T.
|
| タイトル |
Distinct bidirectional regulation of LFA1 and α4β7 by Rap1 and integrin adaptors in T cells under shear flow.
|
| ジャーナル |
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.
|
| 巻・号 |
42(6)
|
| ページ |
112580
|
| 公開日 |
2023-6-1
|
| DOI |
10.1016/j.celrep.2023.112580
|
| PII |
S2211-1247(23)00591-0
|
| PMID |
37267105
|
| IF |
8.109
|
| リソース情報 |
| 遺伝子材料 |
pCAG-HIVgp (RDB04394)
pCMV-VSV-G-RSV-Rev (RDB04393) |
