Septins as membrane influencers: direct play or in association with other cytoskeleton partners

Figures

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  FIGURE 1. Septin structure, assembly and functions related to membranes. (A) Assembly of the septin cytoskeleton. In humans, the septin family comprises 13 members organized into 4 groups (2, 6, 7 and 3) according to their sequence homology. The organization of the four septin group into hexamers and octamers is depicted. Septin monomers either interact through their N- and C-terminal domains (NC/NC interfaces), or through their GTP-binding domain (G/G interfaces). These oligomers can then assemble into filaments or into rings. (B) Structural domains encountered in septin proteins. All the septins exhibit a GTP-binding domain (GBD), a septin unique element (SUE), and N- and C-terminal extensions (NTE, CTE) of variable length. Note that the CTE, which contains one or more coiled-coil regions is absent in group 3 septins. Membrane binding is mediated by two AH (amphipathic helix) and PB (polybasic domain) motifs. SEPT9 exhibits physical binding to F-actin through the first half of its NTE, and to microtubules through its N-terminal K/R-R/x-x-D/E repeat motifs. (C) Septin molecular functions. At the molecular level, septins can form diffusion barriers or act as scaffolds, as illustrated here…

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  FIGURE 2. Impact on membranes of septin interplay with other cytoskeletons (A) Actin-related impacts. While facilitating cell invasion of specific bacteria, septins can also limit invasion either by enhancing host cell rigidity or by favoring autophagy-mediated degradation once bacteria have been internalized. During mesenchymal migration, septins contribute to the stabilization of nascent focal adhesions and to extracellular matrix degradation through metalloproteinase secretion. Septin-mediated enhancement of actomyosin contractility ultimately increase cell tension forces, thereby impacting the tumoral environment and modulating mechano-responsiveness. By linking the catenin complex to the actin cytoskeleton, septins favor cell-cell junctions required for the apico- basal polarity. During cytokinesis, membrane-associated septins and anillin are required to anchor the actomyosin contractile ring to the cell cortex. (B) Microtubule- and ESCRT-related impacts. Septins control the binding and motricity of molecular motors, thereby regulating the retrograde and anterograde transport on microtubules of proteins or vesicles, as illustrated with the clustering of lysosomes during cell…