The state of the septin cytoskeleton from assembly to function

Abstract

Septins are conserved guanine nucleotide-binding proteins that polymerize into filaments at the cell cortex or in association with other cytoskeletal proteins, such as actin or microtubules. As integral players in many morphogenic and signaling events, septins form scaffolds important for the recruitment of the cytokinetic machinery, organization of the plasma membrane, and orientation of cell polarity. Mutations in septins or their misregulation are associated with numerous diseases. Despite growing appreciation for the importance of septins in different aspects of cell biology and disease, septins remain relatively poorly understood compared with other cytoskeletal proteins. Here in this review, we highlight some of the recent developments of the last two years in the field of septin cell biology.

Keywords: Amphipathic helix (AH) domain.

Figure 1.. Subunit order of the mammalian and budding yeast septin complexes.

The original proposed subunit ordering of the mammalian septin complex positioned Sept2 in the middle and Sept7 at the termini, with Sept7’s G-interface facing outward (top left). The subunit ordering has now been revised, with Sept7 positioned in the middle of the hexamer and Sept2 on the outside with its NC-interface facing outward. When present, Sept9 becomes the inner most subunit. This revised mammalian subunit ordering resembles the established ordering of the budding yeast septin complex (right panels). NC: N- and C- terminal interface, G: G-domain interface, CTE: C-terminal extension.

Figure 2.. An amphipathic helix (AH) domain enables septins to recognize micron-scale membrane curvature.

(A) Septins preferentially bind lipid membranes with micron-scale curvature. (B) The penultimate subunit within the complex (e.g. Cdc12 in budding yeast, Sept6 in mammals) harbors an AH domain, which necessary and sufficient for septins to recognize membrane curvature. Inset is a helical wheel diagram of the Cdc12 AH domain (Heliquest). (C) Cartoon representation of an amphipathic helix within a lipid packing defect generated by membrane curvature.

Figure 3.. Subcellular localization of septins through the cell cycle in budding yeast.

Septins (green) localize around the polarity site early in the cell cycle. After bud emergence, septins are arrayed in parallel pairs at the bud neck - the site of positive plasma membrane curvature. Prior to cytokinesis septins rearrange into separate rings on other side of the bud neck and the actomyosin ring (AMR).