Article abstract
Nature Cell Biology 9, 905 - 914 (2007)
Published online: 8 July 2007 | doi:10.1038/ncb1615
Plasma membrane nanoswitches generate high-fidelity Ras signal transduction
Tianhai Tian1,4, Angus Harding1,3,4, Kerry Inder1, Sarah Plowman1, Robert G. Parton1,2 & John F. Hancock1
Abstract
Ras proteins occupy dynamic plasma membrane nanodomains called nanoclusters. The significance of this spatial organization is unknown. Here we show, using in silico and in vivo analyses of mitogen-activated protein (MAP) kinase signalling, that Ras nanoclusters operate as sensitive switches, converting graded ligand inputs into fixed outputs of activated extracellular signal-regulated kinase (ERK). By generating Ras nanoclusters in direct proportion to ligand input, cells build an analogue–digital–analogue circuit relay that transmits a signal across the plasma membrane with high fidelity. Signal transmission is completely dependent on Ras spatial organization and fails if nanoclustering is abrogated. A requirement for high-fidelity signalling may explain the non-random distribution of other plasma membrane signalling complexes.
- Institute for Molecular Bioscience, University of Queensland, Brisbane 4072, Australia.
- Centre for Microscopy and Microanalysis, University of Queensland, Brisbane 4072, Australia.
- Current address: Department of Pathology and Immunology, Washington University, St Louis, Missouri 63015, USA.
- These authors contributed equally to the paper.
Correspondence to: John F. Hancock1 e-mail: j.hancock@imb.uq.edu.au
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