| First Author | Sun H | Year | 2018 |
| Journal | J Cell Biol | Volume | 217 |
| Issue | 4 | Pages | 1453-1465 |
| PubMed ID | 29535192 | Mgi Jnum | J:260483 |
| Mgi Id | MGI:6149638 | Doi | 10.1083/jcb.201707055 |
| Citation | Sun H, et al. (2018) Transmission of integrin beta7 transmembrane domain topology enables gut lymphoid tissue development. J Cell Biol 217(4):1453-1465 |
| abstractText | Integrin activation regulates adhesion, extracellular matrix assembly, and cell migration, thereby playing an indispensable role in development and in many pathological processes. A proline mutation in the central integrin beta3 transmembrane domain (TMD) creates a flexible kink that uncouples the topology of the inner half of the TMD from the outer half. In this study, using leukocyte integrin alpha4beta7, which enables development of gut-associated lymphoid tissue (GALT), we examined the biological effect of such a proline mutation and report that it impairs agonist-induced talin-mediated activation of integrin alpha4beta7, thereby inhibiting rolling lymphocyte arrest, a key step in transmigration. Furthermore, the alpha4beta7(L721P) mutation blocks lymphocyte homing to and development of the GALT. These studies show that impairing the ability of an integrin beta TMD to transmit talin-induced TMD topology inhibits agonist-induced physiological integrin activation and biological function in development. |
