Protein Phase Separation Provides Long-Term Memory of Transient Spatial Stimuli.

TitleProtein Phase Separation Provides Long-Term Memory of Transient Spatial Stimuli.
Publication TypeJournal Article
Year of Publication2018
AuthorsDine, E, Gil, AA, Uribe, G, Brangwynne, CP, Toettcher, JE
JournalCell Syst
Volume6
Issue6
Pagination655-663.e5
Date Published2018 06 27
ISSN2405-4712
KeywordsComputer Simulation, Feedback, Physiological, Membrane Proteins, Memory, Long-Term, Neoplasm Proteins, Optogenetics, Organelles, Proteins, RNA, Signal Transduction, Spatial Memory
Abstract

<p>Protein/RNA clusters arise frequently in spatially regulated biological processes, from the asymmetric distribution of P granules and PAR proteins in developing embryos to localized receptor oligomers in migratory cells. This co-occurrence suggests that protein clusters might possess intrinsic properties that make them a useful substrate for spatial regulation. Here, we demonstrate that protein droplets show a robust form of spatial memory, maintaining the spatial pattern of an inhibitor of droplet formation long after it has been removed. Despite this persistence, droplets can be highly dynamic, continuously exchanging monomers with the diffuse phase. We investigate the principles of biophysical spatial memory in three contexts: a computational model of phase separation; a novel optogenetic system where light can drive rapid, localized dissociation of liquid-like protein droplets; and membrane-localized signal transduction from clusters of receptor tyrosine kinases. Our results suggest that the persistent polarization underlying many cellular and developmental processes could arise through a simple biophysical process, without any additional biochemical feedback loops.</p>

DOI10.1016/j.cels.2018.05.002
Alternate JournalCell Syst
PubMed ID29859829
PubMed Central IDPMC6023754
Grant ListDP2 EB024247 / EB / NIBIB NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States
U01 DA040601 / DA / NIDA NIH HHS / United States