3 research outputs found
Caveolae protect endothelial cells from membrane rupture during increased cardiac output.
Caveolae are strikingly abundant in endothelial cells, yet the physiological functions of caveolae in endothelium and other tissues remain incompletely understood. Previous studies suggest a mechanoprotective role, but whether this is relevant under the mechanical forces experienced by endothelial cells in vivo is unclear. In this study we have sought to determine whether endothelial caveolae disassemble under increased hemodynamic forces, and whether caveolae help prevent acute rupture of the plasma membrane under these conditions. Experiments in cultured cells established biochemical assays for disassembly of caveolar protein complexes, and assays for acute loss of plasma membrane integrity. In vivo, we demonstrate that caveolae in endothelial cells of the lung and cardiac muscle disassemble in response to acute increases in cardiac output. Electron microscopy and two-photon imaging reveal that the plasma membrane of microvascular endothelial cells in caveolin 1(-/-) mice is much more susceptible to acute rupture when cardiac output is increased. These data imply that mechanoprotection through disassembly of caveolae is important for endothelial function in vivo
Organelle dynamics and membrane trafficking in apoptosis and autophagy
The accurate control of cell death is a vital
aspect of development in metazoans and plays crucial
roles in the prevention of disease. Apoptosis is the main
form of regulated cell death in multicellular organisms,
although there are other contributory pathways. During
apoptosis, mammalian cells undergo dramatic changes in
organelle structure ad organisation that define the
apoptotic execution phase. Although the roles of
apoptotic protease machinery (the caspases) in these
rearrangements are quite well understood, the purpose of
organelle disruption during cell death is not yet entirely
appreciated. Indeed, recent evidence implicates caspase
targeting of organellar proteins and subsequent organelle
disruption upstream of apoptotic execution proper,
suggesting the existence of pathways linking organelle
damage to cell death. In this review, we describe the
changes to the endomembrane system that are inherent
during the apoptotic execution phase, and examine the
evidence for endomembrane-mediated pathways towards
apoptotic execution. We also discuss aspects of the
molecular control of autophagy - an important
contributor to a cell’s response to stress, and a membrane
trafficking process whose regulation is linked to the
apoptotic machinery at multiple levels