%0 Journal Article
%T Transmission of integrin ¦Â7 transmembrane domain topology enables gut lymphoid tissue development
%A Alexre R.
%A Alexre R. Gingras
%A Fan
%A Frederic
%A Frederic Lagarrigue
%A Gingras
%A Ginsberg
%A Hao
%A Hao Sun
%A Klaus
%A Klaus Ley
%A Lagarrigue
%A Ley
%A Mark H.
%A Mark H. Ginsberg
%A Sun
%A Zhichao
%A Zhichao Fan
%J JCB | The Journal of Cell Biology
%D 2018
%R 10.1083/jcb.201707055
%X 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 ¦Â3 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 ¦Á4¦Â7, 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 ¦Á4¦Â7, thereby inhibiting rolling lymphocyte arrest, a key step in transmigration. Furthermore, the ¦Á4¦Â7(L721P) mutation blocks lymphocyte homing to and development of the GALT. These studies show that impairing the ability of an integrin ¦Â TMD to transmit talin-induced TMD topology inhibits agonist-induced physiological integrin activation and biological function in development.
%U http://jcb.rupress.org/content/217/4/1453