Hof1 and Chs4 Interact via F-BAR Domain and Sel1-like Repeats to Control Extracellular Matrix Deposition during Cytokinesis

Abstract

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].

The chaperone Chs7 forms a stable complex with Chs3 and promotes its activity at the cell surface

“…However, Chs7 is not needed for chitin synthesis by Chs1 or Chs2, 2 synthases with related catalytic domains. Alternatively, the presence of Chs7 could help Chs3 to maintain its fully active conformation or promote its association with activators such as Chs4 . A final hypothesis is that Chs7 is not an obligatory subunit of a Chs7‐Chs3 chitin synthase complex, but instead interacts reversibly with Chs3 to regulate its activity.…”

“…Palmitoylation of Chs3 by the palmitoyl transferase Pfa4 is needed to prevent aggregation and partial retention of Chs3 in the ER . At the Golgi, Chs3 is recognized by components of exomer, a specialized coat that regulates its export to the cell surface, while other factors such as Chs4 and Bni4 contribute to Chs3 activation and retention at the bud neck . Chs3 transits between the Golgi, bud neck, and endosomes in a cell‐cycle dependent manner and is maintained in intracellular compartments until ready for use …”

Transcriptional responses of the marine green alga Micromonas pusilla and an infecting prasinovirus under different phosphate conditions

“…Twenty‐nine out of the 80 SLR proteins in the M. pusilla genome (van Baren et al ., ) showed increased relative transcript abundance with fold‐changes > 4 in the low‐P treatment. SLR gene activation has been observed under endoplasmic reticulum‐stress‐inducing conditions in other eukaryotes (Mittl and Schneider‐Brachert, ), and one SLR protein controls extracellular matrix deposition during cell division in yeast (Oh et al ., ), but otherwise their functions are not known. Ours is the first report of SLR transcriptional responses in phytoplankton and provides targets for future investigation of how cells modulate and modify division in response to changes in nutrients or potential stress factors.…”

Molecular mechanisms of contractile-ring constriction and membrane trafficking in cytokinesis

“…The cell polarity protein Spa2 is needed for Chs2 to be incorporated into the IPCs (Foltman et al 2018). Hof1 is an important inhibitor of Chs3 to ensure that secondary septum formation does not begin until the ring has constricted and primary septum has been formed (Oh et al 2017). Rho1 is a critical regulator of extracellular matrix remodeling, as it controls the activities of Fsk1 and Chs3, as well as regulating the localization of the exocyst complex (Qadota et al 1996;Guo et al 2001;Valdivia and Schekman 2003).…”