Integrin β₃ directly inhibits the Gα₁₃-p115RhoGEF interaction to regulate G protein signaling and platelet exocytosis.

ABSTRACT: The integrins and G protein-coupled receptors are both fundamental in cell biology. The cross talk between these two, however, is unclear. Here we show that β₃ integrins negatively regulate G protein-coupled signaling by directly inhibiting the Gα₁₃-p115RhoGEF interaction. Furthermore, whereas β₃ deficiency or integrin antagonists inhibit integrin-dependent platelet aggregation and exocytosis (granule secretion), they enhance G protein-coupled RhoA activation and integrin-independent secretion. In contrast, a β₃-derived Gα₁₃-binding peptide or Gα₁₃ knockout inhibits G protein-coupled RhoA activation and both integrin-independent and dependent platelet secretion without affecting primary platelet aggregation. In a mouse model

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC10432399 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature