Tetraspanner‐based nanodomains modulate BAR domain‐induced membrane curvature

Abstract

The topography of biological membranes is critical for formation of protein and lipid microdomains. One prominent example in the yeast plasma membrane (PM) are BAR domain‐induced PM furrows. Here we report a novel function for the Sur7 family of tetraspanner proteins in the regulation of local PM topography. Combining TIRF imaging, STED nanoscopy, freeze–fracture EM and membrane simulations we find that Sur7 tetraspanners form multimeric strands at the edges of PM furrows, where they modulate forces exerted by BAR domain proteins at the furrow base. Loss of Sur7 tetraspanners or Sur7 displacement due to altered PIP2 homeostasis leads to increased PM invagination and a distinct form of membrane tubulation. Physiological defects associated with PM tubulation are rescued by synthetic anchoring of Sur7 to furrows. Our findings suggest a key role for tetraspanner proteins in sculpting local membrane domains. The maintenance of stable PM furrows depends on a balance between negative curvature at the base which is generated by BAR domains and positive curvature at the furrows' edges which is stabilized by strands of Sur7 tetraspanners. image Maintenance of stable PM furrows in budding yeast depends on Sur7 tetraspanner strands at the upper edge that counteract the negative curvature generated by BAR domains at the furrow base. Sur7 tetraspanners in budding yeast form multimeric strands at the edge of PM furrows. Sur7 strands are sensitive to increased PI(4,5)P2 levels and counteract the curvature induced by BAR domain proteins to prevent closure of furrows into tubes. A force balance between tetraspanners and BAR domain proteins ensures maintenance of stable PM furrows.