Profilin's Affinity for Formin Regulates the Availability of Filament Ends for Actin Monomer Binding

Research output: Contribution to journalArticlepeer-review

Abstract

Nucleation-promoting proteins tightly regulate actin polymerization in cells. Whereas many of these proteins bind actin monomers directly, formins use the actin-binding protein profilin to dynamically load actin monomers onto their flexible Formin Homology 1 (FH1) domains. Following binding, FH1 domains deliver profilin-actin complexes to filament ends. To investigate profilin's role as an adaptor protein in formin-mediated elongation, we engineered a chimeric formin that binds actin monomers directly via covalent attachment of profilin to its binding site in the formin. This formin mediates slow filament elongation owing to a high probability of profilin binding at filament ends. Varying the position at which profilin is tethered to the formin alters the elongation rate by modulating profilin occupancy at the filament end. By regulating the availability of the barbed end, we propose that profilin binding establishes a secondary point of control over the rate of filament elongation mediated by formins. Profilin's differential affinities for actin monomers, barbed ends and polyproline are thus tuned to adaptively bridge actin and formins and optimize the rate of actin polymerization.

Original languageEnglish (US)
Article number166688
JournalJournal of Molecular Biology
Volume432
Issue number24
DOIs
StatePublished - Dec 4 2020

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health (NIH) research grant GM-122787 (to N.C.) . M.E.Z. was supported by NIH Training Grant AR007612.

Publisher Copyright:
© 2020 Elsevier Ltd

Keywords

  • Cytoskeleton
  • Fluorescence microscopy
  • Kinetics
  • Polymerization

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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