Human septins organize as octamer-based filaments and mediate actin-membrane anchoring in cells.

Human septins organize as octamer-based filaments and mediate actin-membrane anchoring in cells.
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DOI:
10.1083/jcb.202203016
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发表时间:
2023-03-06
期刊:
The Journal of cell biology
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其他
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Martins et al. show that all septins associated with actin stress fibers organize as octamer-based filaments that mediate actin-membrane anchoring. Depleting octamers or preventing septins from polymerizing leads to a partial loss of stress fibers and compromised cell mechanics. Septins are cytoskeletal proteins conserved from algae and protists to mammals. A unique feature of septins is their presence as heteromeric complexes that polymerize into filaments in solution and on lipid membranes. Although animal septins associate extensively with actin-based structures in cells, whether septins organize as filaments in cells and if septin organization impacts septin function is not known. Customizing a tripartite split-GFP complementation assay, we show that all septins decorating actin stress fibers are octamer-containing filaments. Depleting octamers or preventing septins from polymerizing leads to a loss of stress fibers and reduced cell stiffness. Super-resolution microscopy revealed septin fibers with widths compatible with their organization as paired septin filaments. Nanometer-resolved distance measurements and single-protein tracking further showed that septin filaments are membrane bound and largely immobilized. Finally, reconstitution assays showed that septin filaments mediate actin–membrane anchoring. We propose that septin organization as octamer-based filaments is essential for septin function in anchoring and stabilizing actin filaments at the plasma membrane.
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