Membrane reshaping by micrometric curvature sensitive septin filaments

Abstract

Septins are cytoskeletal filaments that assemble at the inner face of the plasma membrane. They are localized at constriction sites and impact membrane remodeling. We report in vitro tools to examine how yeast septins behave on curved and deformable membranes. Septins reshape the membranes of Giant Unilamellar Vesicles with the formation of periodic spikes, while flattening smaller vesicles. We show that membrane deformations are associated to preferential arrangement of septin filaments on specific curvatures. When binding to bilayers supported on custom-designed periodic wavy patterns displaying positive and negative micrometric radii of curvatures, septin filaments remain straight and perpendicular to the curvature of the convex parts, while bending negatively to follow concave geometries. Based on these results, we propose a theoretical model that describes the deformations and micrometric curvature sensitivity observed in vitro. The model captures the reorganizations of septin filaments throughout cytokinesis in vivo, providing mechanistic insights into cell division.

Interplay of septin amphipathic helices in sensing membrane-curvature and filament bundling

“…Septins can distinguish positive membrane curvatures at the micron-scale without any other cellular factors . When purified septins are mixed with membranes at a range of different curvatures, septins polymerize into aligned filaments wrapped at an optimal curvature (Beber et al, 2019;Cannon et al, 2019;Tanaka-Takiguchi et al, 2009). However, individual septin complexes can distinguish membranes with micron-scale curvature which manifests through septin-membrane binding kinetics (Cannon et al, 2019).…”

Septin Roles and Mechanisms in Organization of Endothelial Cell Junctions

“…Septin proteins and filaments are known to interact directly with membrane lipids 13,[70][71][72]78 , accumulating at locations with positive curvature 18,79,80 . This direct interaction can be mediated by a polybasic region of septins interacting with acidic head groups of phospholipids on the membrane surface 81 .…”

Role of septins in microbial infection

“…Bin-Amphiphysin-Rvs domain-containing proteins) that detect curvature at the nanometer scale (McMahon and Boucrot, 2015). Interestingly, new work has shown that an amphipathic helix (AH) is necessary and sufficient for septin curvature sensing both in vitro and in vivo (Cannon et al, 2019), and that septin filaments can reorganize in response to changes in membrane curvature (Beber et al, 2019). Considering their important roles in health and disease (Hall and Russell, 2004;Mostowy and Cossart, 2012;Peterson and Petty, 2010), how septins assemble and how they work in conjunction with actin, microtubules and phospholipids, are the focus of intense investigation.…”