Caveolae and lipid sorting: Shaping the cellular response to stress

Abstract

Caveolae are an abundant and characteristic surface feature of many vertebrate cells. The uniform shape of caveolae is characterized by a bulb with consistent curvature connected to the plasma membrane (PM) by a neck region with opposing curvature. Caveolae act in mechanoprotection by flattening in response to increased membrane tension, and their disassembly influences the lipid organization of the PM. Here, we review evidence for caveolae as a specialized lipid domain and speculate on mechanisms that link changes in caveolar shape and/or protein composition to alterations in specific lipid species. We propose that high membrane curvature in specific regions of caveolae can enrich specific lipid species, with consequent changes in their localization upon caveolar flattening. In addition, we suggest how changes in the association of lipid-binding caveolar proteins upon flattening of caveolae could allow release of specific lipids into the bulk PM. We speculate that the caveolae-lipid system has evolved to function as a general stress-sensing and stress-protective membrane domain.

Minimizing isotropic and deviatoric membrane energy – An unifying formation mechanism of different cellular membrane nanovesicle types

“…Due to specific composition of rafts, also their local curvature may be different than in other membrane regions. Indeed, such formations also called caveolae were observed in experiments [59] indicating that curvature underlays a sorting mechanism connecting the shape and the composition of biological membranes. Recently, it was observed that endocytosis in diverse cell types was connected to formation of membrane domains [53].…”

Energy and Dynamics of Caveolae Trafficking

“…The plasma membranes of endothelial, muscle, and fat cells are packed with caveolae, suggesting an important role in specialized functions including homeostasis and metabolism. Caveolae also comprise a specific lipid environment containing large amounts of cholesterol, sphingomyelin, and ceramides (Graf et al, 1999 ; Parton et al, 2020b ; Zhou et al, 2020 ). These lipids accumulate in caveolae, providing a reservoir for these molecules (Hubert et al, 2020b ).…”

CHIMs are versatile cholesterol analogs mimicking and visualizing cholesterol behavior in lipid bilayers and cells

“…As CHIM-L behaves similarly to cholesterol in model membranes, we next tested whether this is also observed in the membrane system of live cells. We first concentrated on caveolae, which represent cholesterol-rich PM invaginations functioning for instance as mechanosensors and cellular signaling regulators 22 , 23 . Cholesterol is recruited to such raft-like areas by interaction with the prime protein constituent caveolin1 (Cav1) 23 and serves a structural role as removal of cholesterol causes disruption and flattening of caveolae 24 , 25 .…”