Using optogenetics to interrogate the dynamic control of signal transmission by the Ras/Erk module.

TitleUsing optogenetics to interrogate the dynamic control of signal transmission by the Ras/Erk module.
Publication TypeJournal Article
Year of Publication2013
AuthorsToettcher, JE, Weiner, OD, Lim, WA
JournalCell
Volume155
Issue6
Pagination1422-34
Date Published2013 Dec 5
ISSN1097-4172
KeywordsAnimals, Cells, MAP Kinase Signaling System, Mice, NIH 3T3 Cells, Optogenetics, Paracrine Communication, PC12 Cells, ras Proteins, Rats, Single-Cell Analysis, STAT3 Transcription Factor
Abstract

<p>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.</p>

DOI10.1016/j.cell.2013.11.004
Alternate JournalCell
PubMed ID24315106
PubMed Central IDPMC3925772
Grant ListGM084040 / GM / NIGMS NIH HHS / United States
GM096164 / GM / NIGMS NIH HHS / United States
GM55040 / GM / NIGMS NIH HHS / United States
GM62583 / GM / NIGMS NIH HHS / United States
P50 GM081879 / GM / NIGMS NIH HHS / United States
P50GM081879 / GM / NIGMS NIH HHS / United States
PN2EY016546 / EY / NEI NIH HHS / United States
R01 GM055040 / GM / NIGMS NIH HHS / United States
R01 GM084040 / GM / NIGMS NIH HHS / United States
R01 GM096164 / GM / NIGMS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
/ / Howard Hughes Medical Institute / United States