Spatiotemporal Regulation of FMNL2 by N-Terminal Myristoylation and C-Terminal Phosphorylation Drives Rapid Filopodia Formation

Biomolecules. 2023 Mar 17;13(3):548. doi: 10.3390/biom13030548.

Abstract

The actin nucleating and polymerizing formin-like 2 (FMNL2) is upregulated in several cancers and has been shown to play important roles in cell migration, invasion, cell-cell adhesion and filopodia formation. Here, using structured illumination microscopy we show that FMNL2 promotes rapid and highly dynamic filopodia formation in epithelial cells while remaining on the tip of the growing filopodia. This filopodia tip localization depends fully on its N-terminal myristoylation. We further show that FMNL2-dependent filopodia formation requires its serine 1072 phosphorylation within the diaphanous-autoregulatory domain (DAD) by protein kinase C (PKC) α. Consistent with this, filopodia formation depends on PKC activity and PKCα localizes to the base of growing filopodia. Thus, a PKCα-FMNL2 signaling module spatiotemporally controls dynamic filopodia formation.

Keywords: FMNL2; actin; filopodia; formins; protein kinase C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Cell Movement
  • Formins* / metabolism
  • Humans
  • Phosphorylation
  • Protein Kinase C-alpha* / metabolism
  • Pseudopodia* / metabolism

Substances

  • Actins
  • Protein Kinase C-alpha
  • FMNL2 protein, human
  • Formins

Grants and funding

R.G. was funded by the DFG under Germany’s Excellence Strategy (EXC-2189, project ID 390939984). C.S. was funded with a research grant by the DFG (project: 444519856).