title: Using optogenetics to interrogate the dynamic control of signal transmission by the Ras/Erk module.
abstract: The complex, interconnected architecture of cell-signaling networks makes it challenging to disentangle how cells process extracellular information to make decisions. We have developed an optogenetic approach to selectively activate isolated intracellular signaling nodes with light and use this method to follow the flow of information from the signaling protein Ras. By measuring dose and frequency responses in single cells, we characterize the precision, timing, and efficiency with which signals are transmitted from Ras to Erk. Moreover, we elucidate how a single pathway can specify distinct physiological outcomes: by combining distinct temporal patterns of stimulation with proteomic profiling, we identify signaling programs that differentially respond to Ras dynamics, including a paracrine circuit that activates STAT3 only after persistent (>1 hr) Ras activation. Optogenetic stimulation provides a powerful tool for analyzing the intrinsic transmission properties of pathway modules and identifying how they dynamically encode distinct outcomes.
authors: Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158-2517, USA; Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158-2517, USA; Department of Biochemistry, University of California San Francisco, San Francisco, CA 94158-2517, USA.
authors: Jared E
authors: JE
authors: Toettcher
authors: Orion D
authors: OD
authors: Weiner
authors: Wendell A
authors: WA
authors: Lim
mesh_terms: D000818:Animals; D002477:Cells / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D041681:NIH 3T3 Cells; D062308:Optogenetics / Q000379:methods*; D016716:PC12 Cells; D019899:Paracrine Communication; D051381:Rats; D050796:STAT3 Transcription Factor / Q000378:metabolism; D059010:Single-Cell Analysis / Q000379:methods*; D018631:ras Proteins / Q000378:metabolism
chemical_list: D050796:STAT3 Transcription Factor; D018631:ras Proteins