Direct Rap1/Talin1 interaction regulates platelet and neutrophil integrin activity in mice.

ABSTRACT: Targeting Talin1 to the plasma membrane is a crucial step in integrin activation, which in leukocytes is mediated by a Rap1/RIAM/Talin1 pathway, whereas in platelets, it is RIAM independent. Recent structural, biochemical, and cell biological studies have suggested direct Rap1/Talin1 interaction as an alternative mechanism to recruit Talin1 to the membrane and induce integrin activation. To test whether this pathway is of relevance in vivo, we generated Rap1 binding-deficient Talin1 knockin (Tln1^3mut) mice. Although Tln1^3mut mice showed no obvious abnormalities, their platelets exhibited reduced integrin activation, aggregation, adhesion, and spreading, resulting in prolonged tail-bleeding times and delayed thrombus formation and vessel occlusion in vivo. Surprisingly

SUBMITTER: Bromberger T 

PROVIDER: S-EPMC6307989 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature