Kuo, Chun-Chen, Savage, Natasha S ORCID: 0000-0002-6831-6533, Chen, Hsin, Wu, Chi-Fang, Zyla, Trevin R and Lew, Daniel J
(2014)
Inhibitory GEF Phosphorylation Provides Negative Feedback in the Yeast Polarity Circuit.
Current Biology, 24 (7).
pp. 753-759.
Text
2014_Kuo_CurrBiol.pdf - Author Accepted Manuscript Download (2MB) |
Abstract
Cell polarity is critical for the form and function of many celltypes. During polarity establishment, cells define a cortical‘‘front’’ that behaves differently from the rest of the cortex.The front accumulates high levels of the active form ofa polarity-determining Rho-family GTPase (Cdc42, Rac, orRop) that then orients cytoskeletal elements through variouseffectors to generate the polarized morphology appropriateto the particular cell type [1, 2]. GTPase accumulation isthought to involve positive feedback, such that activeGTPase promotes further delivery and/or activation ofmore GTPase in its vicinity [3]. Recent studies suggest thatonce a front forms, the concentration of polarity factors atthe front can increase and decrease periodically, first clus-tering the factors at the cortex and then dispersing themback to the cytoplasm [4–7]. Such oscillatory behaviorimplies the presence of negative feedback in the polaritycircuit [8], but the mechanism of negative feedback wasnot known. Here we show that, in the budding yeastSaccha-romyces cerevisiae, the catalytic activity of the Cdc42-directed GEF is inhibited by Cdc42-stimulated effectorkinases, thus providing negative feedback. We furthershow that replacing the GEF with a phosphosite mutantGEF abolishes oscillations and leads to the accumulationof excess GTP-Cdc42 and other polarity factors at the front.These findings reveal a mechanism for negative feedbackand suggest that the function of negative feedback via GEFinhibition is to buffer the level of Cdc42 at the polarity site.
Item Type: | Article |
---|---|
Additional Information: | ## TULIP Type: Articles/Papers (Journal) ## |
Uncontrolled Keywords: | Saccharomyces cerevisiae, cdc42 GTP-Binding Protein, Saccharomyces cerevisiae, Guanine Nucleotide Exchange Factors, Signal Transduction, Cell Polarity, Phosphorylation, Models, Biological, Computer Simulation, Feedback, Physiological |
Depositing User: | Symplectic Admin |
Date Deposited: | 10 Apr 2017 06:53 |
Last Modified: | 19 Jan 2023 07:34 |
DOI: | 10.1016/j.cub.2014.02.024 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3002232 |