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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 of myocardial ischemia/reperfusion injury in vivo, the β₃-derived Gα₁₃-binding peptide inhibits platelet secretion of granule constituents, which exacerbates inflammation and ischemia/reperfusion injury. These data establish crucial integrin-G protein crosstalk, providing a rationale for therapeutic approaches that inhibit exocytosis in platelets and possibly other cells without adverse effects associated with loss of cell adhesion.

SUBMITTER: Zhang Y

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

REPOSITORIES: biostudies-literature

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

Zhang Yaping Y Zhao Xiaojuan X Shen Bo B Bai Yanyan Y Chang Claire C Stojanovic Aleksandra A Wang Can C Mack Andrew A Deng Gary G Skidgel Randal A RA Cheng Ni N Du Xiaoping X

Nature communications 20230816 1

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 ...[more]

PMID: 37587112

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Dataset Information

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

Publications

Integrin β<sub>3</sub> directly inhibits the Gα<sub>13</sub>-p115RhoGEF interaction to regulate G protein signaling and platelet exocytosis.

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