Article ; Online: Cavin-1/PTRF mediates insulin-dependent focal adhesion remodeling and ameliorates high-fat diet-induced inflammatory responses in mice.
The Journal of biological chemistry
2019 Volume 294, Issue 27, Page(s) 10544–10552
Abstract: 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 ... ...
| Abstract | 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. |
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| MeSH term(s) | 3T3-L1 Cells ; Animals ; Caveolae/metabolism ; Caveolin 1/deficiency ; Caveolin 1/genetics ; Caveolin 1/metabolism ; Diet, High-Fat ; Focal Adhesions/drug effects ; Focal Adhesions/metabolism ; Inflammation/etiology ; Inflammation/metabolism ; Insulin/pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Paxillin/metabolism ; Protein Binding ; Signal Transduction ; Stress, Mechanical |
| Chemical Substances | Caveolin 1 ; Insulin ; Paxillin |
| Language | English |
| Publishing date | 2019-05-24 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural |
| ZDB-ID | 2997-x |
| ISSN | 1083-351X ; 0021-9258 |
| ISSN (online) | 1083-351X |
| ISSN | 0021-9258 |
| DOI | 10.1074/jbc.RA119.008824 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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