Phosphorylation of the F-BAR protein Hof1 drives septin ring splitting in budding yeast

Abstract

Abstract A double septin ring at the division site accompanies cytokinesis in yeasts and mammalian cells. In budding yeast, reorganisation of the septin collar at the bud neck into a dynamic double ring, a process we refer to as septin ring splitting, is an essential prerequisite for constriction of the actomyosin ring and, ultimately, for cytokinesis. Septin ring splitting involves the selective disassembly of septin filaments at the bud neck and requires the Mitotic Exit Network (MEN), a Hippo-like kinase cascade essential for cytokinesis. However, the effectors of MEN in this process are unknown. Here we identify the F-BAR protein Hof1 as a critical target of MEN in septin ring splitting. Phospho-mimicking HOF1 mutant alleles overcome the septin splitting defects due to MEN inactivation by decreasing Hof1 binding to septins and facilitating its translocation to the cytokinetic actomyosin ring. Hof1-mediated septin ring splitting depends upon its F-BAR domain, suggesting that it may involve a local membrane reorganisation that leads to septin disassembly. In vitro reconstitution assays show that Hof1 can induce the formation of large networks of intertwined septin bundles, while a phosphomimetic Hof1 protein has impaired septin-bundling activity, likely due to its decreased affinity for septins. Altogether, our data indicate that Hof1 modulates septin architecture in distinct ways depending on its phosphorylation status.