Eisosome-driven plasma membrane organization is mediated by BAR domains

Abstract

Plasma membranes are organized into domains of different protein and lipid composition. Eisosomes are key complexes for yeast plasma membrane organization, containing primarily Pil1 and Lsp1. Here we show that both proteins consist mostly of a banana-shaped BAR domain common to membrane sculpting proteins, most similar to the ones of amphiphysin, arfaptin 2 and endophilin 2. Our data reveal a previously unrecognized family of BAR-domain proteins involved in plasma membrane organization.

Eisosomes Regulate Phosphatidylinositol 4,5-Bisphosphate (PI(4,5)P2) Cortical Clusters and Mitogen-activated Protein (MAP) Kinase Signaling upon Osmotic Stress

“…Beyond positioning, we speculate that eisosomes may play a role in cluster assembly and/or turnover. The lipids encased within a cellular eisosome are unknown, but the core eisosome protein Pil1 binds preferentially to negatively charged lipids including PI 4-phosphate and PI(4,5)P 2 in vitro (4,(7)(8)(9). Thus, eisosomes may inhibit PI(4,5)P 2 cluster formation by sequestering this phospholipid or its precursor PI 4-phosphate.…”

“…Recent studies have also uncovered eisosome structures at the plasma membrane of microalgae and lichens (6). The core component of yeast eisosomes is a BAR domain protein called Pil1, which directly binds to lipids and provides structural curvature to these plasma membrane invaginations (7)(8)(9).…”

Eisosome Ultrastructure and Evolution in Fungi, Microalgae, and Lichens

“…High sterol concentrations increase the viscosity of membrane interiors (97,98). We therefore suggest that once yeast eisosomal BAR proteins are tethered to plasma membranes by their electrostatic targeting signals (6,28), the uncoiling and the posited association of their nonpolar domains with the membrane interior can generate regular striations in the ergosterol-rich phase of the membrane, an ordering that may not readily be imposed on a more fluid fatty acid-rich phase.…”

“…Additional proteins also associate with these punctate domains, in some cases in a transient fashion (17), and the MCC component is reportedly enriched in ergosterol (18) and influenced by phosphoinositide (6,19,20) and sphingolipid (14,17,(21)(22)(23)(24) levels. Hence, the current yeast model (25,26) proposes that Pil1p and Lsp1p, which contain membrane curvatureinducing BAR domains (6,27,28), together with Seg1p (29,30), form a submembrane complex (6) reportedly influenced by Pil1p phosphorylation (25); this complex then either creates or associates with the MCC domains, presumably inducing an inward curvature. The MCC protein Nce102p has also been implicated in generating curvature (5,31).…”

Assembly of fission yeast eisosomes in the plasma membrane of budding yeast: Import of foreign membrane microdomains

“…Structures morphologically identical with the furrows of MCC were frequently reported by freeze-etching studies in organisms possessing cell walls, from bacteria to plants (summarized in (Stradalova et al, 2009)). It was shown that core eisosomal proteins, BAR domain-containing Pil1 and its homologue Lsp1, form large tubular aggregates and tubulate liposomes in vitro Olivera-Couto et al, 2011;Ziolkowska et al, 2011). High resolution electron microscopy views of the plasma membrane furrows suggested that in vivo these proteins assemble into hemitubular scaffold.…”