We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Integrin β<sub>3</sub> directly inhibits the Gα<sub>13</sub>-p115RhoGEF interaction to regulate G protein signaling and platelet exocytosis.
- Authors
Zhang, Yaping; Zhao, Xiaojuan; Shen, Bo; Bai, Yanyan; Chang, Claire; Stojanovic, Aleksandra; Wang, Can; Mack, Andrew; Deng, Gary; Skidgel, Randal A.; Cheng, Ni; Du, Xiaoping
- 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. Zhang et al. show that the adhesion receptor integrin β3 directly inhibits G protein mediated RhoA activation and granule secretion. A peptide mimicking this effect selectively inhibits platelet secretion but not integrin-mediated platelet adhesion.
- Subjects
G protein coupled receptors; MYOCARDIAL reperfusion; CELL adhesion; BLOOD platelet aggregation; G proteins; BLOOD platelets; EXOCYTOSIS; CYTOLOGY; INTEGRINS
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-40531-3