Spatiotemporal distribution of PKCα, Cdc42, and Rac1 before directed cell migration

Biochem Biophys Res Commun. 2021 Dec 20;584:26-31. doi: 10.1016/j.bbrc.2021.10.080. Epub 2021 Nov 2.

Abstract

Cdc42 is a key factor in directed cell migration and accumulates at the leading edge of migrating cells. However, what kind of proteins control Cdc42 and when is unclear. After mechanical wounding, protein kinase C α (PKCα), a conventional PKC isozyme, begins to accumulate at the edges of cells adjacent to the wounded cells (WCs). In this study, we hypothesized that PKCα may be implicated in directed cell migration at an early stage before Cdc42 controls the migration. We focused on the spatiotemporal distribution of PKCα, Cdc42, and Rac1 before cell migration. After wounding, at the edges of cells adjacent to the WCs, PKCα accumulation, Cdc42 accumulation, Rac1 accumulation, and filopodia formation occurred in that order. The PKCα inhibitor suppressed Cdc42 accumulation at the cell edges. These results suggest that inhibition of PKCα activity inhibits cell migration. In addition, it is not Cdc42 but PKCα that may decide the direction of cell migration.

Keywords: Cdc42; Cell migration; Protein kinase Cα; Rac1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bryostatins / pharmacology
  • Calcium / metabolism
  • Cell Movement*
  • Cells, Cultured
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism*
  • Keratinocytes / cytology
  • Keratinocytes / metabolism*
  • Microscopy, Fluorescence / methods
  • Protein Kinase C-alpha / genetics
  • Protein Kinase C-alpha / metabolism*
  • Rats
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Stress, Mechanical
  • Time-Lapse Imaging / methods
  • cdc42 GTP-Binding Protein / genetics
  • cdc42 GTP-Binding Protein / metabolism*
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism*

Substances

  • Bryostatins
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins
  • Protein Kinase C-alpha
  • Rac1 protein, rat
  • cdc42 GTP-Binding Protein
  • rac1 GTP-Binding Protein
  • Calcium