title: Daughter cell identity emerges from the interplay of Cdc42, septins, and exocytosis.
abstract: Asymmetric cell division plays a crucial role in cell differentiation, unequal replicative senescence, and stem cell maintenance. In budding yeast, the identities of mother and daughter cells begin to diverge at bud emergence when distinct plasma-membrane domains are formed and separated by a septin ring. However, the mechanisms underlying this transformation remain unknown. Here, we show that septins recruited to the site of polarization by Cdc42-GTP inhibit Cdc42 activity in a negative feedback loop, and this inhibition depends on Cdc42 GTPase-activating proteins. Combining live-cell imaging and computational modeling, we demonstrate that the septin ring is sculpted by polarized exocytosis, which creates a hole in the accumulating septin density and relieves the inhibition of Cdc42. The nascent ring generates a sharp boundary that confines the Cdc42 activity and exocytosis strictly to its enclosure and thus clearly delineates the daughter cell identity. Our findings define a fundamental mechanism underlying eukaryotic cell fate differentiation.
authors.affiliation: Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okada
authors.forename: Marcin
authors.initials: M
authors.lastname: Leda
authors.forename: Julia
authors.initials: J
authors.lastname: Hanna
authors.forename: Natasha S
authors.initials: NS
authors.lastname: Savage
authors.forename: Erfei
authors.initials: E
authors.lastname: Bi
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Goryachev
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology*; D025461:Feedback, Physiological; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D058112:Septins / Q000378:metabolism*; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D029701:Saccharomyces cerevisiae Proteins; D058112:Septins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae
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