Author: ["Anchal Chandra","Hernán E. Grecco","Venkat Pisupati","David Perera","Liam Cassidy","Ferdinandos Skoulidis","Shehab A. Ismail","Christian Hedberg","Michael Hanzal-Bayer","Ashok R. Venkitaraman","Alfred Wittinghofer","Philippe I. H. Bastiaens"]
CITE.CC academic search helps you expand the influence of your papers.
Abstract
We identify a role for the GDI-like solubilizing factor (GSF) PDEδ in modulating signalling through Ras family G proteins by sustaining their dynamic distribution in cellular membranes. We show that the GDI-like pocket of PDEδ binds and solubilizes farnesylated Ras proteins, thereby enhancing their diffusion in the cytoplasm. This mechanism allows more effective trapping of depalmitoylated Ras proteins at the Golgi and polycationic Ras proteins at the plasma membrane to counter the entropic tendency to distribute these proteins over all intracellular membranes. Thus, PDEδ activity augments K/Hras signalling by enriching Ras at the plasma membrane; conversely, PDEδ down-modulation randomizes Ras distributions to all membranes in the cell and suppresses regulated signalling through wild-type Ras and also constitutive oncogenic Ras signalling in cancer cells. Our findings link the activity of PDEδ in determining Ras protein topography to Ras-dependent signalling. Bastiaens and colleagues find that PDEδ can solubilize Ras family small GTPases, resulting in their release from cellular membranes. This concentrates Ras proteins at specific subcellular locations, which promotes their eventual association with the plasma membrane and potentiates Ras-mediated signal transduction.Cite this article
Chandra, A., Grecco, H., Pisupati, V. et al. The GDI-like solubilizing factor PDEδ sustains the spatial organization and signalling of Ras family proteins. Nat Cell Biol 14, 148–158 (2012). https://doi.org/10.1038/ncb2394 