Mechanism of integrin activation by talin and its cooperation with kindlin

• DOI: 10.1038/s41467-022-30117-w
• Publication Date: 2022-04-29T10:05:34Z
• Authors: Fan Lu; Liang Zhu; Thomas Bromberger; Jun Yang; Qiannan Yang; Jianmin Liu; Edward F. Plow; Markus Moser; Jun Qin
• Keywords: Paxillin; RGD motif

Abstract Talin-induced integrin binding to extracellular matrix ligands (integrin activation) is the key step trigger many fundamental cellular processes including cell adhesion, migration, and spreading. Talin widely known use its N-terminal head domain (talin-H) bind activate integrin, but how talin-H operates in context of full-length talin surrounding remains unknown. Here we show that while being capable inducing activation, alone exhibits unexpectedly low potency versus a constitutively activated talin. We find large C-terminal rod (talin-R), which otherwise masks site on inactive talin, dramatically enhances by dimerizing bridging it co-activator kindlin-2 via adaptor protein paxillin. These data provide crucial insight into mechanism cooperation with kindlin promote potent signaling.