Cavin-1/PTRF mediates insulin-dependent focal adhesion remodeling and ameliorates high-fat diet-induced inflammatory...

Cavin-1/polymerase I and transcript release factor (PTRF) is a requisite component of caveolae, small plasma membrane invaginations that are highly abundant in adipocytes. Cavin-1 is a dynamic molecule whose dissociation from caveolae plays an important role in mechanoprotection and rRNA synthesis. In the former situation, the acute dissociation of cavin-1 from caveolae allows cell membrane expansion that occurs upon insulin-aided lipid uptake into the fat cells. Cavin-1 dissociation from caveolae and membrane flattening alters the cytoskeleton and the interaction of plasma membrane proteins with the extracellular matrix through interactions with focal adhesion structures. Here, using cavin-1 knockout mice, subcellular fractionation, and immunoblotting methods, we addressed the relationship of cavin-1 with focal adhesion complexes following nutritional stimulation. We found that cavin-1 is acutely translocated to focal complex compartments upon insulin stimulation, where it regulates focal complex formation through an interaction with paxillin. We found that loss of cavin-1 impairs focal complex remodeling and focal adhesion formation and causes a mechanical stress response, concomitant with activation of proinflammatory and senescence/apoptosis pathways. We conclude that cavin-1 plays key roles in dynamic remodeling of focal complexes upon metabolic stimulation. This mechanism also underlies the crucial role of caveolae in the long-term healthy expansion of the adipocyte.