한빛사 논문
Jeongmin Ju,1,2,7 Hae Nim Lee,1,3,7 Lin Ning,4,5 Hyunjoo Ryu,1 Xin X. Zhou,4,5 Hyeyeon Chun,1 Yong Woo Lee,1 Austin I. Lee-Richerson,4 Cherlhyun Jeong,6 Michael Z. Lin,4,5,* and Jihye Seong1,2,3,4,8,*
1Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea
2Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea
3Department of Converging Science and Technology, Kyung Hee University, Seoul 02453, Republic of Korea
4Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
5Department of Neurobiology, Stanford University, Stanford, CA 94305, USA
6Center for Theragnosis, Korea Institute of Science and Technology, Seoul 02792, South Korea
7These authors contributed equally
8Lead contact
*Correspondence
Abstract
How protein signaling networks respond to different input strengths is an important but poorly understood problem in cell biology. For example, RhoA can promote focal adhesion (FA) growth or disassembly, but how RhoA activity mediates these opposite outcomes is not clear. Here, we develop a photoswitchable RhoA guanine nucleotide exchange factor (GEF), psRhoGEF, to precisely control endogenous RhoA activity. Using this optical tool, we discover that peak FA disassembly selectively occurs upon activation of RhoA to submaximal levels. We also find that Src activation at FAs selectively occurs upon submaximal RhoA activation, identifying Src as an amplitude-dependent RhoA effector. Finally, a pharmacological Src inhibitor reverses the direction of the FA response to RhoA activation from disassembly to growth, demonstrating that Src functions to suppress FA growth upon RhoA activation. Thus, rheostatic control of RhoA activation by psRhoGEF reveals that cells can use signal amplitude to produce multiple responses to a single biochemical signal.
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