Cavin-1/PTRF mediates insulin-dependent focal adhesion remodeling and ameliorates high-fat diet–induced inflammatory responses in mice
Autor: | Libin Liu, Hong Wang, Paul F. Pilch |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Caveolin 1 Caveolae Diet High-Fat Biochemistry Cell membrane Focal adhesion Mice 03 medical and health sciences PTRF 3T3-L1 Cells medicine Animals Insulin Molecular Biology Lipid raft Paxillin Inflammation Mice Knockout Focal Adhesions 030102 biochemistry & molecular biology biology Chemistry Cell Biology Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Membrane protein biology.protein Stress Mechanical Protein Binding Signal Transduction Cavin |
Zdroj: | J Biol Chem |
ISSN: | 0021-9258 |
Popis: | 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. |
Databáze: | OpenAIRE |
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