Actin polymerization counteracts prewetting of N-WASP on supported lipid bilayers

Proc Natl Acad Sci U S A. 2024 Dec 10;121(50):e2407497121. doi: 10.1073/pnas.2407497121. Epub 2024 Dec 4.

Abstract

Cortical condensates, transient punctate-like structures rich in actin and the actin nucleation pathway member Neural Wiskott-Aldrich syndrome protein (N-WASP), form during activation of the actin cortex in the Caenorhabditis elegans oocyte. Their emergence and spontaneous dissolution is linked to a phase separation process driven by chemical kinetics. However, the mechanisms that drive the onset of cortical condensate formation near membranes remain unexplored. Here, using a reconstituted phase separation assay of cortical condensate proteins, we demonstrate that the key component, N-WASP, can collectively undergo surface condensation on supported lipid bilayers via a prewetting transition. Actin partitions into the condensates, where it polymerizes and counteracts the N-WASP prewetting transition. Taken together, the dynamics of condensate-assisted cortex formation appear to be controlled by a balance between surface-assisted condensate formation and polymer-driven condensate dissolution. This opens perspectives for understanding how the formation of complex intracellular structures is affected and controlled by phase separation.

Keywords: cortical condensates; in vitro actin cortices; prewetting.

MeSH terms

  • Actins* / chemistry
  • Actins* / metabolism
  • Animals
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / metabolism
  • Caenorhabditis elegans* / metabolism
  • Lipid Bilayers* / chemistry
  • Lipid Bilayers* / metabolism
  • Oocytes / metabolism
  • Polymerization*
  • Wiskott-Aldrich Syndrome Protein, Neuronal* / chemistry
  • Wiskott-Aldrich Syndrome Protein, Neuronal* / metabolism

Substances

  • Lipid Bilayers
  • Actins
  • Wiskott-Aldrich Syndrome Protein, Neuronal
  • Caenorhabditis elegans Proteins