Rho signaling participates in membrane fluidity homeostasis.
Preservation of both the integrity and fluidity of biological membranes is a critical cellular homeostatic function. Signaling pathways that govern lipid bilayer fluidity have long been known in bacteria, yet no such pathways have been identified in eukaryotes. Here we identify mutants of the yeast Saccharomyces cerevisiae whose growth is differentially influenced by its two principal unsaturated fatty acids, oleic and palmitoleic acid. Strains deficient in the core components of the cell wall integrity (CWI) pathway, a MAP kinase pathway dependent on both Pkc1 (yeast's sole protein kinase C) and Rho1 (the yeast RhoA-like small GTPase), were among those inhibited by palmitoleate yet stimulated by oleate. A single GEF (Tus1) and a single GAP (Sac7) of Rho1 were also identified, neither of which participate in the CWI pathway. In contrast, key components of the CWI pathway, such as Rom2, Bem2 and Rlm1, failed to influence fatty acid sensitivity. The differential influence of palmitoleate and oleate on growth of key mutants correlated with changes in membrane fluidity measured by fluorescence anisotropy of TMA-DPH, a plasma membrane-bound dye. This work provides the first evidence for the existence of a signaling pathway that enables eukaryotic cells to control membrane fluidity, a requirement for division, differentiation and environmental adaptation.
Department of Biochemistry, University of Washington, Seattle, Washington, United States of America.
Daniel
D
Lockshon
Carissa Perez
CP
Olsen
Christopher L
CL
Brett
Andrei
A
Chertov
Alexey J
AJ
Merz
Daniel A
DA
Lorenz
Marc R
MR
Van Gilst
Brian K
BK
Kennedy
D005229:Fatty Acids, Monounsaturated / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D008560:Membrane Fluidity / Q000502:physiology*; D019301:Oleic Acid / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000502:physiology*
D005229:Fatty Acids, Monounsaturated; D029701:Saccharomyces cerevisiae Proteins; C008757:palmitoleic acid; D019301:Oleic Acid; C490702:PKC1 protein, S cerevisiae; D011493:Protein Kinase C; C051302:RHO1 protein, S cerevisiae; D020741:rho GTP-Binding Proteins