Caveolae are bulb-shaped, cholesterol-rich plasma membrane (PM) invaginations with a wide array of functions, including lipid turnover and PM organisation. PASCIN-2, a member of the membrane-shaping F-BAR protein family, localises to the neck of caveolae and has thus been proposed to be involved in membrane deformations associated with their morphogenesis. However, the role of lipid composition in caveolae formation remains unclear, and in this study, Akio Kitao, Shiro Suetsugu and co-workers (Gusmira et al., 2020) use liposomes that mimic the phospholipid and cholesterol content of caveolae to examine in detail PASCIN2-mediated membrane shaping. Interestingly, they found that cholesterol reduces the binding affinity of PASCIN2 for liposomes and thus inhibits the formation of membrane tubules. Conversely, the formation of tubules with caveolin-1 at their tips, suggestive of intermediates of caveolae endocytosis, was enhanced when cholesterol was depleted from liposomes. In agreement with this, knockout of PASCIN2 in HeLa cells resulted in the reduced removal of caveolae from the PM when cholesterol was acutely depleted. Taken together, these findings point to a role for PASCIN2 in removing cholesterol-free caveolae from the PM, which might be important for the maintenance of cholesterol-enriched caveolae at the cell surface.
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