Supersensitive Ras activation in dendrites and spines revealed by two-photon fluorescence lifetime imaging

Yasuda, Ryohei, Harvey, Christopher D., Zhong, Haining, Sobczyk, Aleksander, Van Aelst, Linda, Svoboda, Karel (2006) Supersensitive Ras activation in dendrites and spines revealed by two-photon fluorescence lifetime imaging. Nature Neuroscience, 9 (2). pp. 283-291. ISSN 10976256

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URL: http://www.ncbi.nlm.nih.gov/pubmed/16429133

DOI: 10.1038/nn1635

Abstract

To understand the biochemical signals regulated by neural activity, it is necessary to measure protein-protein interactions and enzymatic activity in neuronal microcompartments such as axons, dendrites and their spines. We combined two-photon excitation laser scanning with fluorescence lifetime imaging to measure fluorescence resonance energy transfer at high resolutions in brain slices. We also developed sensitive fluorescent protein-based sensors for the activation of the small GTPase protein Ras with slow (FRas) and fast (FRas-F) kinetics. Using FRas-F, we found in CA1 hippocampal neurons that trains of back-propagating action potentials rapidly and reversibly activated Ras in dendrites and spines. The relationship between firing rate and Ras activation was highly nonlinear (Hill coefficient ?5). This steep dependence was caused by a highly cooperative interaction between calcium ions (Ca2+) and Ras activators. The Ras pathway therefore functions as a supersensitive threshold detector for neural activity and Ca2+ concentration. © 2006 Nature Publishing Group.

Item Type:	Paper
Uncontrolled Keywords:	Ras protein dendrite dendritic spine fluorescence microscopy supersensitivity Diagnostic Imaging
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > GTPase organs, tissues, organelles, cell types and functions > tissues types and functions > axon Investigative techniques and equipment > microscopy > flourescence microscopy organs, tissues, organelles, cell types and functions > tissues types and functions > hippocampus Investigative techniques and equipment > optical devices > lasers Investigative techniques and equipment > optical devices > lasers > two-photon excitation laser scanning
CSHL Authors:	Harvey, Christopher D. Svoboda, Karel Van Aelst, Linda
Communities:	CSHL labs > Svoboda lab CSHL labs > Van Aelst lab School of Biological Sciences > Publications
Depositing User:	CSHL Librarian
Date:	2006
Date Deposited:	05 Dec 2011 21:26
Last Modified:	19 Sep 2014 18:53
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/22940

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