Stoichiometry controls activity of phase-separated clusters of actin signaling proteins

Lindsay B. Case, Xu Zhang, Jonathon A. Ditlev, Michael K Rosen

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Biomolecular condensates concentrate macromolecules into foci without a surrounding membrane. Many condensates appear to form through multivalent interactions that drive liquid-liquid phase separation (LLPS). LLPS increases the specific activity of actin regulatory proteins toward actin assembly by the Arp2/3 complex. We show that this increase occurs because LLPS of the Nephrin-Nck-N-WASP signaling pathway on lipid bilayers increases membrane dwell time of N-WASP and Arp2/3 complex, consequently increasing actin assembly. Dwell time varies with relative stoichiometry of the signaling proteins in the phase-separated clusters, rendering N-WASP and Arp2/3 activity stoichiometry dependent. This mechanism of controlling protein activity is enabled by the stoichiometrically undefined nature of biomolecular condensates. Such regulation should be a general feature of signaling systems that assemble through multivalent interactions and drive nonequilibrium outputs.

Original languageEnglish (US)
Pages (from-to)1093-1097
Number of pages5
JournalScience (New York, N.Y.)
Volume363
Issue number6431
DOIs
StatePublished - Mar 8 2019

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Actin-Related Protein 2-3 Complex
Actins
Proteins
Membranes
Lipid Bilayers

ASJC Scopus subject areas

  • General

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Stoichiometry controls activity of phase-separated clusters of actin signaling proteins. / Case, Lindsay B.; Zhang, Xu; Ditlev, Jonathon A.; Rosen, Michael K.

In: Science (New York, N.Y.), Vol. 363, No. 6431, 08.03.2019, p. 1093-1097.

Research output: Contribution to journalArticle

Case, Lindsay B. ; Zhang, Xu ; Ditlev, Jonathon A. ; Rosen, Michael K. / Stoichiometry controls activity of phase-separated clusters of actin signaling proteins. In: Science (New York, N.Y.). 2019 ; Vol. 363, No. 6431. pp. 1093-1097.
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