Developmental Cell
Volume 26, Issue 2, 29 July 2013, Pages 148-161
Journal home page for Developmental Cell

Article
Daughter Cell Identity Emerges from the Interplay of Cdc42, Septins, and Exocytosis

https://doi.org/10.1016/j.devcel.2013.06.015Get rights and content
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Highlights

  • Septins provide negative feedback to Cdc42 activity that depends on Cdc42 GAPs

  • Septin ring is formed by highly focused polarized exocytosis

  • Suppression of exocytosis causes chasing behavior of septins

  • Septin ring size is primarily determined by size of the underlying Cdc42 cluster

Summary

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.

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These authors contributed equally to this work

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Present address: Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, UK