GxcM-Fbp17/RacC-WASP signaling regulates polarized cortex assembly in migrating cells via Arp2/3

J Cell Biol. 2023 Jun 5;222(6):e202208151. doi: 10.1083/jcb.202208151. Epub 2023 Apr 3.

Abstract

The actin-rich cortex plays a fundamental role in many cellular processes. Its architecture and molecular composition vary across cell types and physiological states. The full complement of actin assembly factors driving cortex formation and how their activities are spatiotemporally regulated remain to be fully elucidated. Using Dictyostelium as a model for polarized and rapidly migrating cells, we show that GxcM, a RhoGEF localized specifically in the rear of migrating cells, functions together with F-BAR protein Fbp17, a small GTPase RacC, and the actin nucleation-promoting factor WASP to coordinately promote Arp2/3 complex-mediated cortical actin assembly. Overactivation of this signaling cascade leads to excessive actin polymerization in the rear cortex, whereas its disruption causes defects in cortical integrity and function. Therefore, apart from its well-defined role in the formation of the protrusions at the cell front, the Arp2/3 complex-based actin carries out a previously unappreciated function in building the rear cortical subcompartment in rapidly migrating cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / genetics
  • Actin-Related Protein 2-3 Complex / metabolism
  • Actins* / metabolism
  • Dictyostelium* / genetics
  • Dictyostelium* / metabolism
  • Protozoan Proteins* / genetics
  • Protozoan Proteins* / metabolism
  • Signal Transduction
  • Wiskott-Aldrich Syndrome Protein / metabolism

Substances

  • Actin-Related Protein 2-3 Complex
  • Actins
  • Wiskott-Aldrich Syndrome Protein
  • Protozoan Proteins