Plasma membrane nanoswitches generate high-fidelity Ras signal transduction

Tian, T., Harding, A., Inder, K., Plowman, S., Parton, R.G. and Hancock, J.F. (2007) Plasma membrane nanoswitches generate high-fidelity Ras signal transduction. Nature Cell Biology, 9, pp. 905-914. (doi: 10.1038/ncb1615)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Tian, Dr Tianhai
• Authors: Tian, T., Harding, A., Inder, K., Plowman, S., Parton, R.G., and Hancock, J.F.
• Subjects: Q Science > QH Natural history > QH345 Biochemistry
• College/School: College of Science and Engineering > School of Mathematics and Statistics > Mathematics
• Journal Name: Nature Cell Biology
• ISSN: 1465-7392
• ISSN (Online): 1476-4679
• Published Online: 08 July 2007