A link between mitotic entry and membrane growth suggests a novel model for cell size control

Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
The Journal of Cell Biology (Impact Factor: 9.83). 03/2012; 197(1):89-104. DOI: 10.1083/jcb.201108108
Source: PubMed


Addition of new membrane to the cell surface by membrane trafficking is necessary for cell growth. In this paper, we report that blocking membrane traffic causes a mitotic checkpoint arrest via Wee1-dependent inhibitory phosphorylation of Cdk1. Checkpoint signals are relayed by the Rho1 GTPase, protein kinase C (Pkc1), and a specific form of protein phosphatase 2A (PP2A(Cdc55)). Signaling via this pathway is dependent on membrane traffic and appears to increase gradually during polar bud growth. We hypothesize that delivery of vesicles to the site of bud growth generates a signal that is proportional to the extent of polarized membrane growth and that the strength of the signal is read by downstream components to determine when sufficient growth has occurred for initiation of mitosis. Growth-dependent signaling could explain how membrane growth is integrated with cell cycle progression. It could also control both cell size and morphogenesis, thereby reconciling divergent models for mitotic checkpoint function.

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Available from: Douglas R Kellogg
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    • "Note that the real contribution of Pkc1 to septin ring stability under normal conditions might be underestimated in our experiments by the addition to the medium of sorbitol, which we show stabilizes septins at the bud neck. In our hands, conditional pkc1 mutant cells (Anastasia et al., 2012; unpublished data) rapidly lose viability and lyse in the absence of osmostabilizers similar to pkc1Δ cells, thus hampering a rigorous assessment of the effect of Pkc1 on septin regulation. We cannot exclude that Rho1 contributes to septin ring assembly and stabilization also via additional effectors besides Pkc1. "
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    ABSTRACT: In many cell types septins assemble into filaments and rings at the neck of cellular appendages and/or at the cleavage furrow to help compartmentalize the plasma membrane and support cytokinesis. How septin ring assembly is coordinated with membrane remodelling and controlled by mechanical stress at these sites is however unclear.Through a genetic screen we uncovered an unanticipated link between the conserved Rho1 GTPase and its effector protein kinase C (Pkc1) with septin ring stability in yeast. Both Rho1 and Pkc1 stabilize the septin ring, at least partly through phosphorylation of the membrane-associated F-BAR protein Syp1, which colocalizes asymmetrically with the septin ring at the bud neck. Syp1 is displaced from the bud neck upon Pkc1-dependent phosphorylation at two serines, thereby impacting the rigidity of the new-forming septin ring. We propose that Rho1 and Pkc1 coordinate septin ring assembly with membrane and cell wall remodelling partly by controlling Syp1 residence at the bud neck. © 2015 by The American Society for Cell Biology.
    Full-text · Article · Jul 2015 · Molecular biology of the cell
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    ABSTRACT: Study identifies a signaling pathway that may control cell size by linking membrane transport to mitotic entry.
    Preview · Article · Apr 2012 · The Journal of Cell Biology

  • No preview · Article · Apr 2012 · Nature Reviews Molecular Cell Biology
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