Actin-induced hyperactivation of the Ras signaling pathway leads to apoptosis in Saccharomyces cerevisiae

Ayscough, K. and Gourlay, C.W. (2006) Actin-induced hyperactivation of the Ras signaling pathway leads to apoptosis in Saccharomyces cerevisiae. Molecular and Cellular Biology, 26(17), pp. 6487-6501. (doi:10.1128/MCB.00117-06)

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Abstract

Recent research has revealed a conserved role for the actin cytoskeleton in the regulation of aging and apoptosis among eukaryotes. Here we show that the stabilization of the actin cytoskeleton caused by deletion of Sla1p or End3p leads to hyperactivation of the Ras signaling pathway. The consequent rise in cyclic AMP (cAMP) levels leads to the loss of mitochondrial membrane potential, accumulation of reactive oxygen species (ROS), and cell death. We have established a mechanistic link between Ras signaling and actin by demonstrating that ROS production in actin-stabilized cells is dependent on the G-actin binding region of the cyclase-associated protein Srv2p/CAP. Furthermore, the artificial elevation of cAMP directly mimics the apoptotic phenotypes displayed by actin-stabilized cells. The effect of cAMP elevation in inducing actin-mediated apoptosis functions primarily through the Tpk3p subunit of protein kinase A. This pathway represents the first defined link between environmental sensing, actin remodeling, and apoptosis in Saccharomyces cerevisiae.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:UNSPECIFIED
Authors: Ayscough, K., and Gourlay, C.W.
College/School:College of Medical Veterinary and Life Sciences
Journal Name:Molecular and Cellular Biology
ISSN:0270-7306
ISSN (Online):1098-5549

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
296121The regulation and coupling of endocytosis to dynamic changes in the actin cytoskeletonKathryn AyscoughMedical Research Council (MRC)G117/394Biochemistry & Cell Biology