Abstract
Septins are a highly conserved family of proteins that form palindromic hetero-oligomeric rods, which anneal into non-polar filaments. Via association with the plasma membrane, septin filaments recognize micron-scale membrane curvature, create diffusion barriers, and regulate cell morphogenic events via scaffolding other cytoskeletal polymers (i.e., filamentous actin [F-actin] and microtubules) and biochemical regulators of cell division, cell migration, and polarity establishment.1,2 Although interaction with cellular membranes is thought to be crucial for septin polymer dynamics and function, how septins associate with membranes is not understood. Three polybasic regions (PB1, PB2, and PB3) and an amphipathic helix (AH) are each sufficient for membrane interaction in vitro, and while the AH domain has been implicated in conferring membrane curvature sensing in vivo in the filamentous fungus Ashbya, the functionality of these domains in the context of intact septin complexes in vivo is still incompletely defined.3,4,5,6,7,8,9 We identified and characterized an isoform of Caenorhabditis elegans septin UNC-61 that was predicted to contain a transmembrane domain (TMD; UNC-61a). UNC-61a was expressed in a subset of tissues where the known septins act, and the TMD was required for tissue integrity of the egg-laying apparatus. We found predicted TMD-containing septins across much of opisthokont phylogeny and demonstrated that the TMD-containing sequence of a primate TMD-septin is sufficient for localization to cellular membranes. Together, our findings reveal a novel mechanism of septin-membrane association with profound implications for septin dynamics and regulation.