Cholesterol Depletion in Adipocytes Causes Caveolae Collapse Concomitant with Proteosomal Degradation of Cavin-2 in a Switch-Like Fashion

Caveolae, little caves of cell surfaces, are enriched in cholesterol, a certain level of which is required for their structural integrity. Here we show in adipocytes that cavin-2, a peripheral membrane protein and one of 3 cavin isoforms present in caveolae from non-muscle tissue, is degraded upon cholesterol depletion in a rapid fashion resulting in collapse of caveolae. We exposed 3T3-L1 adipocytes to the cholesterol depleting agent methyl-β-cyclodextrin, which results in a sudden and extensive degradation of cavin-2 by the proteasome and a concomitant movement of cavin-1 from the plasma membrane to the cytosol along with loss of caveolae. The recovery of cavin-2 at the plasma membrane is cholesterol-dependent and is required for the return of cavin-1 from the cytosol to the cell surface and caveolae restoration. Expression of shRNA directed against cavin-2 also results in a cytosolic distribution of cavin-1 and loss of caveolae. Taken together, these data demonstrate that cavin-2 functions as a cholesterol responsive component of caveolae that is required for cavin-1 localization to the plasma membrane, and caveolae structural integrity

The analysis of DMD gene deletions by multiplex PCR in Indonesian DMD/BMD patients: The era of personalized medicine

10.1186/s13104-019-4730-1BMC Research Notes121704-complete

Caveola-forming proteins caveolin‑1 and PTRF in prostate cancer

The expression of caveola-forming proteins is dysregulated in prostate cancer. Caveolae are flask-shaped invaginations of the plasma membrane that have roles in membrane trafficking and cell signalling. Members of two families of proteins-caveolins and cavins-are known to be required for the formation and functions of caveolae. Caveolin-1, the major structural protein of caveolae, is overexpresssed in prostate cancer and has been demonstrated to be involved in prostate cancer angiogenesis, growth and metastasis. Polymerase I and transcript release factor (PTRF) is the only cavin family member necessary for caveola formation. When exogenously expressed in prostate cancer cells, PTRF reduces aggressive potential, probably via both caveola-mediated and caveola-independent mechanisms. In addition, stromal PTRF expression decreases with progression of the disease. Evaluation of caveolin-1 antibodies in the clinical setting is underway and it is hoped that future studies will reveal the mechanisms of PTRF action, allowing its targeting for therapeutic purposes

Caveolae as plasma membrane sensors, protectors and organizers

Caveolae are submicroscopic, plasma membrane pits that are abundant in many mammalian cell types. The past few years have seen a quantum leap in our understanding of the formation, dynamics and functions of these enigmatic structures. Caveolae have now emerged as vital plasma membrane sensors that can respond to plasma membrane stresses and remodel the extracellular environment. Caveolae at the plasma membrane can be removed by endocytosis to regulate their surface density or can be disassembled and their structural components degraded. Coat proteins, called cavins, work together with caveolins to regulate the formation of caveolae but also have the potential to dynamically transmit signals that originate in caveolae to various cellular destinations. The importance of caveolae as protective elements in the plasma membrane, and as membrane organizers and sensors, is highlighted by links between caveolae dysfunction and human diseases, including muscular dystrophies and cancer