Electrical properties of plasma membrane modulate subcellular distribution of K-Ras

Gomez, Guillermo A. and Daniotti, Jose L. (2007) Electrical properties of plasma membrane modulate subcellular distribution of K-Ras. The Federation of European Biochemical Societies (FEBS) Journal, 274 9: 2210-2228. doi:10.1111/j.1742-4658.2007.05758.x


Author Gomez, Guillermo A.
Daniotti, Jose L.
Title Electrical properties of plasma membrane modulate subcellular distribution of K-Ras
Journal name The Federation of European Biochemical Societies (FEBS) Journal   Check publisher's open access policy
ISSN 1742-464X
1742-4658
Publication date 2007-05-01
Year available 2007
Sub-type Article (original research)
DOI 10.1111/j.1742-4658.2007.05758.x
Volume 274
Issue 9
Start page 2210
End page 2228
Total pages 19
Place of publication Oxford, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
K-Ras is a small G-protein, localized mainly at the inner leaflet of the plasma membrane. The membrane targeting signal of this protein consists of a polybasic C-terminal sequence of six contiguous lysines and a farnesylated cysteine. Results from biophysical studies in model systems suggest that hydrophobic and electrostatic interactions are responsible for the membrane binding properties of K-Ras. To test this hypothesis in a cellular system, we first evaluated in vitro the effect of electrolytes on K-Ras membrane binding properties. Results demonstrated the electrical and reversible nature of K-Ras binding to anionic lipids in membranes. We next investigated membrane binding and subcellular distribution of K-Ras after disruption of the electrical properties of the outer and inner leaflets of plasma membrane and ionic gradients through it. Removal of sialic acid from the outer plasma membrane caused a redistribution of K-Ras to recycling endosomes. Inhibition of polyphosphoinositide synthesis at the plasma membrane, by depletion of cellular ATP, resulted in a similar subcellular redistribution of K-Ras. Treatment of cells with ionophores that modify transmembrane potential caused a redistribution of K-Ras to cytoplasm and endomembranes. Ca2+ ionophores, compared to K+ ionophores, caused a much broader redistribution of K-Ras to endomembranes. Taken together, these results reveal the dynamic nature of interactions between K-Ras and cellular membranes, and indicate that subcellular distribution of K-Ras is driven by electrostatic interaction of the polybasic region of the protein with negatively charged membranes.
Keyword Calcium
Membrane potential
Polyphosphoinositides
RAS
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
Institute for Molecular Bioscience - Publications
 
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Created: Thu, 20 Oct 2011, 06:36:42 EST by Guillermo Gomez on behalf of Institute for Molecular Bioscience