Caveolin-1 and cavin1 act synergistically to generate a unique lipid environment in caveolae

Caveolae are specialized domains of the vertebrate cell surface with a well-defined morphology and crucial roles in cell migration and mechanoprotection. Unique compositions of proteins and lipids determine membrane architectures. The precise caveolar lipid profile and the roles of the major caveolar structural proteins, caveolins and cavins, in selectively sorting lipids have not been defined. Here, we used quantitative nanoscale lipid mapping together with molecular dynamic simulations to define the caveolar lipid profile. We show that caveolin-1 (CAV1) and cavinl individually sort distinct plasma membrane lipids. Intact caveolar structures composed of both CAV1 and cavin1 further generate a unique lipid nano-environment. The caveolar lipid sorting capability includes selectivities for lipid headgroups and acyl chains. Because lipid headgroup metabolism and acyl chain remodeling are tightly regulated, this selective lipid sorting may allow caveolae to act as transit hubs to direct communications among lipid metabolism, vesicular trafficking, and signaling.

Automated summary

Caveolae, specialized domains of the cell membrane, play crucial roles in lipid sorting and creating a unique lipid environment. Caveolin-1 (CAV1) and cavinl sort distinct plasma membrane lipids individually, while together they generate a unique lipid nano-environment. The selective lipid sorting by caveolae, regulated by lipid metabolism and acyl chain remodeling, may facilitate communication among lipid metabolism, vesicular trafficking, and signaling.