| First Author | Huang M | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 6 | Pages | 112667 |
| PubMed ID | 37330909 | Mgi Jnum | J:338432 |
| Mgi Id | MGI:7511315 | Doi | 10.1016/j.celrep.2023.112667 |
| Citation | Huang M, et al. (2023) LRP12 is an endogenous transmembrane inactivator of alpha4 integrins. Cell Rep 42(6):112667 |
| abstractText | Dynamic regulation of integrin activation and inactivation is critical for precisely controlled cell adhesion and migration in physiological and pathological processes. The molecular basis for integrin activation has been intensively studied; however, the understanding of integrin inactivation is still limited. Here, we identify LRP12 as an endogenous transmembrane inhibitor for alpha4 integrin activation. The LRP12 cytoplasmic domain directly binds to the integrin alpha4 cytoplasmic tail and inhibits talin binding to the beta subunit, thus keeping integrin inactive. In migrating cells, LRP12-alpha4 interaction induces nascent adhesion (NA) turnover at the leading-edge protrusion. Knockdown of LRP12 leads to increased NAs and enhanced cell migration. Consistently, LRP12-deficient T cells show an enhanced homing capability in mice and lead to aggravated chronic colitis in a T cell-transfer colitis model. Altogether, LRP12 is a transmembrane inactivator for integrins that inhibits alpha4 integrin activation and controls cell migration by maintaining balanced NA dynamics. |
