The eisosome core is composed of BAR domain proteins

OLIVERA-COUTO, A.; GRAÑA, M.; HARISPE, L. AND AGUILAR, P.S.

MOLECULAR BIOLOGY OF THE CELL

AMER SOC CELL BIOLOGY

Año: 2011 vol. 22 p. 2360 - 2372

1059-1524

Eisosomes define sites of plasma membrane organization. In Saccharomyces cerevisiae, eisosomes delimit furrow-like plasma membrane invaginations that concentrate sterols, transporters, and signaling molecules. Eisosomes are static macromolecular assem- blies composed of cytoplasmic proteins, most of which have no known function. In this study, we used a bioinformatics approach to analyze a set of 20 eisosome proteins. We found that the core components of eisosomes, paralogue proteins Pil1 and Lsp1, are distant homo- logues of membrane-sculpting Bin/amphiphysin/Rvs (BAR) proteins. Consistent with this find- ing, purified recombinant Pil1 and Lsp1 tubulated liposomes and formed tubules when the proteins were overexpressed in mammalian cells. Structural homology modeling and site- directed mutagenesis indicate that Pil1 positively charged surface patches are needed for membrane binding and liposome tubulation. Pil1 BAR domain mutants were defective in both eisosome assembly and plasma membrane domain organization. In addition, we found that eisosome-associated proteins Slm1 and Slm2 have F-BAR domains and that these do- mains are needed for targeting to furrow-like plasma membrane invaginations. Our results support a model in which BAR domain protein?mediated membrane bending leads to clus- tering of lipids and proteins within the plasma membrane.