| First Author | Ueda Y | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 8 | Pages | 107292 |
| PubMed ID | 37520697 | Mgi Jnum | J:346047 |
| Mgi Id | MGI:7517809 | Doi | 10.1016/j.isci.2023.107292 |
| Citation | Ueda Y, et al. (2023) Rap1 organizes lymphocyte front-back polarity via RhoA signaling and talin1. iScience 26(8):107292 |
| abstractText | Lymphocyte trafficking requires fine-tuning of chemokine-mediated cell migration. This process depends on cytoskeletal dynamics and polarity, but its regulation remains elusive. We quantitatively measured cell polarity and revealed critical roles performed by integrin activator Rap1 in this process, independent of substrate adhesion. Rap1-deficient naive T cells exhibited impaired abilities to reorganize the actin cytoskeleton into pseudopods and actomyosin-rich uropods. Rap1-GTPase activating proteins (GAPs), Rasa3 and Sipa1, maintained an unpolarized shape; deletion of these GAPs spontaneously induced cell polarization, indicative of the polarizing effect of Rap1. Rap1 activation required F-actin scaffolds, and stimulated RhoA activation and actomyosin contractility at the rear. Furthermore, talin1 acted on Rap1 downstream effectors to promote actomyosin contractility in the uropod, which occurred independently of substrate adhesion and talin1 binding to integrins. These findings indicate that Rap1 signaling to RhoA and talin1 regulates chemokine-stimulated lymphocyte polarization and chemotaxis in a manner independent of adhesion. |
