@article{2a58e4259821482185712f4c824e171c,
title = "Phase transitions in the assembly of multivalent signalling proteins",
abstract = "Cells are organized on length scales ranging from {\aa}ngstr{\"o}m to micrometres. However, the mechanisms by which {\"a}ngstr{\"o}m-scale molecular properties are translated to micrometre-scale macroscopic properties are not well understood. Here we show that interactions between diverse synthetic, multivalent macromolecules (including multi-domain proteins and RNA) produce sharp liquid-liquid-demixing phase separations, generating micrometre-sized liquid droplets in aqueous solution. This macroscopic transition corresponds to a molecular transition between small complexes and large, dynamic supramolecular polymers. The concentrations needed for phase transition are directly related to the valency of the interacting species. In the case of the actin-regulatory protein called neural Wiskott-Aldrich syndrome protein (N-WASP) interacting with its established biological partners NCK and phosphorylated nephrin, the phase transition corresponds to a sharp increase in activity towards an actin nucleation factor, the Arp2/3 complex. The transition is governed by the degree of phosphorylation of nephrin, explaining how this property of the system can be controlled to regulatory effect by kinases. The widespread occurrence of multivalent systems suggests that phase transitions may be used to spatially organize and biochemically regulate information throughout biology.",
author = "Pilong Li and Sudeep Banjade and Cheng, {Hui Chun} and Soyeon Kim and Baoyu Chen and Liang Guo and Marc Llaguno and Hollingsworth, {Javoris V.} and King, {David S.} and Banani, {Salman F.} and Russo, {Paul S.} and Jiang, {Qiu Xing} and Nixon, {B. Tracy} and Rosen, {Michael K.}",
note = "Funding Information: Acknowledgements We thank J. Onuchic and S. Padrick for discussion of the theoretical aspects of this study, L. Rice for sharing his fluorescence microscope, M. Socolich for a gift of purified eGFP, K. Luby-Phelps and A. Bugde for advice on FRAP experiments, S. Padrick and L. Doolittle for help in purifying actin and the Arp2/3 complex and forsharingreagents,N.GrishinandS.Shifor helpwithdatabasesearches, K. Lynch for providing the PTB expression construct, D. Billadeau and T. Gomez for providing antibodies, A. Ramesh, W. Winkler and P.-L. Tsai for advice on RNA experiments, K. Roybal and C. W{\"u}lfing for sharing unpublished data, and J. Liu for help with cryo-electron tomography. This work was supported by the following: the Howard Hughes Medical Institute and grants from the National Institutes of Health (NIH) (R01-GM56322) and Welch Foundation (I–1544) to M.K.R., a Chilton Foundation Fellowship to H.-C.C., an NIH EUREKA award (R01-GM088745) to Q.-X.J., an NIH Cancer Biology T32 Training Grant to M.L., a National Science Foundation award (DMR-1005707) to P.S.R. and a Gates Millennium Fund award to J.V.H. Use of the Advanced Photon Source was supported by the US Department of Energy, Basic",
year = "2012",
month = mar,
day = "15",
doi = "10.1038/nature10879",
language = "English (US)",
volume = "483",
pages = "336--340",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7389",
}