Cytokinesis requires coordination of actomyosin ring (AMR) contraction with rearrangements of the plasma membrane and extracellular matrix. In Saccharomyces cerevisiae, new membrane, the chitin synthase Chs2 (which forms the primary septum [PS]), and the protein Inn1 are all delivered to the division site upon mitotic exit even when the AMR is absent. Inn1 is essential for PS formation but not for Chs2 localization. The Inn1 C-terminal region is necessary for localization, and distinct PXXP motifs in this region mediate functionally important interactions with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore PS formation in inn1Δ cells). The Inn1 N terminus resembles C2 domains but does not appear to bind phospholipids; nonetheless, when overexpressed or fused to Hof1, it can provide Inn1 function even in the absence of the AMR. Thus, Inn1 and Cyk3 appear to cooperate in activating Chs2 for PS formation, which allows coordination of AMR contraction with ingression of the cleavage furrow.

Hof1 targets to the division site by interacting with septins and myosin II sequentially during the cell cycle. It plays a role in cytokinesis by coupling actomyosin ring constriction to primary septum formation through interactions with Myo1 and Chs2.

SUMMARY Localized extracellular matrix (ECM) remodeling is thought to stabilize the cleavage furrow and maintain cell shape during cytokinesis [1–14]. This remodeling is spatiotemporally coordinated with a cytoskeletal structure pertaining to a kingdom of life, for example, the FtsZ ring in bacteria [15], the phragmoplast in plants [16], and the actomyosin ring in fungi and animals [17, 18]. While the cytoskeletal structures have been analyzed extensively, the mechanisms of ECM remodeling remain poorly understood. In the budding yeast Saccharomyces cerevisiae, the ECM remodeling refers to sequential formations of the primary and secondary septa that are catalyzed by chitin synthase-II (Chs2) and chitin synthase-III (the catalytic subunit Chs3 and its activator Chs4), respectively [18, 19]. Surprisingly, both Chs2 and Chs3 are delivered to the division site at the onset of cytokinesis [6, 20]. What keeps Chs3 inactive until secondary septum formation remains unknown. Here, we show that Hof1 binds to the Sel1-like repeats (SLR) of Chs4 via its F-BAR domain, and inhibits Chs3-mediated chitin synthesis during cytokinesis. In addition, Hof1 is required for rapid accumulation as well as efficient removal of Chs4 at the division site. This study uncovers a mechanism by which Hof1 controls timely activation of Chs3 during cytokinesis, and defines a novel interaction and function for the conserved F-BAR domain and SLR that are otherwise known for their abilities to bind membrane lipids [21, 22] and scaffold protein complex formation [23].

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