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Oscillatory Dynamics of Cdc42 GTPase in the Control of Polarized Growth

Science  13 Jul 2012:
Vol. 337, Issue 6091, pp. 239-243
DOI: 10.1126/science.1218377

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Pole to Pole

How do fission yeast cells decide when to grow at a single end (or pole) of the cell or whether to grow in a multipolar manner? Das et al. (p. 239, published online 17 May) found that accumulation of the active form of the small guanine nucleotide–binding protein Cdc42 at the growing tip of the cell oscillated with a period of a few minutes. In cells growing at one pole, the oscillations were primarily present at that pole and during bipolar growth symmetrical anticorrelated oscillations were observed. Dynamic competition for Cdc42 between multiple growth zones could represent a flexible mechanism to modulate cell growth asymmetry.

Abstract

Cells promote polarized growth by activation of Rho-family protein Cdc42 at the cell membrane. We combined experiments and modeling to study bipolar growth initiation in fission yeast. Concentrations of a fluorescent marker for active Cdc42, Cdc42 protein, Cdc42-activator Scd1, and scaffold protein Scd2 exhibited anticorrelated fluctuations and oscillations with a 5-minute average period at polarized cell tips. These dynamics indicate competition for active Cdc42 or its regulators and the presence of positive and delayed negative feedbacks. Cdc42 oscillations and spatial distribution were sensitive to the amounts of Cdc42-activator Gef1 and to the activity of Cdc42-dependent kinase Pak1, a negative regulator. Feedbacks regulating Cdc42 oscillations and spatial self-organization appear to provide a flexible mechanism for fission yeast cells to explore polarization states and to control their morphology.

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