Light-based feedback for controlling intracellular signaling dynamics

The ability to apply precise inputs to signaling species in live cells would be transformative for interrogating and understanding complex cell-signaling systems. Here we report an 'optogenetic' method for applying custom signaling inputs using feedback control of a light-gated protein-protein interaction. We applied this strategy to perturb protein localization and phosphoinositide 3-kinase activity, generating time-varying signals and clamping signals to buffer against cell-to-cell variability or changes in pathway activity.

[1]  A. Hodgkin,et al.  Measurement of current‐voltage relations in the membrane of the giant axon of Loligo , 1952, The Journal of physiology.

[2]  AC Tose Cell , 1993, Cell.

[3]  R. Mulligan,et al.  A stable human-derived packaging cell line for production of high titer retrovirus/vesicular stomatitis virus G pseudotypes. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Mark J. Schnitzer,et al.  Single kinesin molecules studied with a molecular force clamp , 1999, Nature.

[5]  T. Meyer,et al.  Spatial Sensing in Fibroblasts Mediated by 3′ Phosphoinositides , 2000, The Journal of cell biology.

[6]  E. Huq,et al.  A light-switchable gene promoter system , 2002, Nature Biotechnology.

[7]  E. Huq,et al.  A Novel Molecular Recognition Motif Necessary for Targeting Photoactivated Phytochrome Signaling to Specific Basic Helix-Loop-Helix Transcription Factorsw⃞ , 2004, The Plant Cell Online.

[8]  宁北芳,et al.  疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A , 2005 .

[9]  Yi-shin Su,et al.  Phytochrome structure and signaling mechanisms. , 2006, Annual review of plant biology.

[10]  Tobias Meyer,et al.  Rapid Chemically Induced Changes of PtdIns(4,5)P2 Gate KCNQ Ion Channels , 2006, Science.

[11]  A. Pühler,et al.  Molecular systems biology , 2007 .

[12]  J. Botto,et al.  The plant cell , 2007, Plant Molecular Biology Reporter.

[13]  Jerome T. Mettetal,et al.  The Frequency Dependence of Osmo-Adaptation in Saccharomyces cerevisiae , 2008, Science.

[14]  J. Chory,et al.  Genetically encoded photoswitching of actin assembly through the Cdc42-WASP-Arp2/3 complex pathway , 2008, Proceedings of the National Academy of Sciences.

[15]  Amy B Tyszkiewicz,et al.  Activation of protein splicing with light in yeast , 2008, Nature Methods.

[16]  A. Oudenaarden,et al.  A Systems-Level Analysis of Perfect Adaptation in Yeast Osmoregulation , 2009, Cell.

[17]  D. G. Gibson,et al.  Enzymatic assembly of DNA molecules up to several hundred kilobases , 2009, Nature Methods.

[18]  R. Rosenfeld Nature , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[19]  Christopher A. Voigt,et al.  Spatiotemporal Control of Cell Signalling Using A Light-Switchable Protein Interaction , 2009, Nature.

[20]  Nico Stuurman,et al.  Computer Control of Microscopes Using µManager , 2010, Current protocols in molecular biology.

[21]  H. Berg,et al.  A modular gradient-sensing network for chemotaxis in Escherichia coli revealed by responses to time-varying stimuli , 2010, Molecular systems biology.

[22]  Jared E Toettcher,et al.  Light control of plasma membrane recruitment using the Phy-PIF system. , 2011, Methods in enzymology.