Paxillin binding to the PH domain of kindlin-3 in platelets is required to support integrin αIIbβ3 outside-in signaling.

ABSTRACT:

Background

Kindlin-3 is essential for supporting the bidirectional signaling of integrin αIIbβ3 in platelets by bridging the crosstalk between integrin αIIbβ3 and the cytoplasmic signaling adaptors.

Objective

In this study, we identified a previously unrecognized paxillin binding site in the pleckstrin homology (PH) domain of kindlin-3 and verified its functional significance.

Methods

Structure-based approaches were employed to identify the paxillin binding site in the PH domain of kindlin-3. In addition, the bidirectional signaling of integrin αIIbβ3 were evaluated in both human and mouse platelets.

Results

In brief, we found that a β1-β2 loop in the PH domain of kindlin-3, an important part of the canonical membrane phospholipid binding pocket, was also invol

SUBMITTER: Nguyen HTT 

PROVIDER: S-EPMC9080902 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature