A Ruthenium(II) Polypyridyl Complex Disrupts Actin Cytoskeleton Assembly and Blocks Cytokinesis

Angew Chem Int Ed Engl. 2022 Jul 4;61(27):e202117449. doi: 10.1002/anie.202117449. Epub 2022 May 3.

Abstract

The dinuclear RuII complex [(Ru(phen)2 )2 (tpphz)]4+ (phen=1,10-phenanthroline, tpphz=tetrapyridophenazine) "RuRuPhen" blocks the transformation of G-actin monomers to F-actin filaments with no disassembly of pre-formed F-actin. Molecular docking studies indicate multiple RuRuPhen molecules bind to the surface of G-actin but not the binding pockets of established actin polymerisation inhibitors. In cells, addition of RuRuPhen causes rapid disruption to actin stress fibre organisation, compromising actomyosin contractility and cell motility; due to this effect RuRuPhen interferes with late-stage cytokinesis. Immunofluorescent microscopy reveals that RuRuPhen causes cytokinetic abscission failure by interfering with endosomal sorting complexes required for transport (ESCRT) complex recruitment.

Keywords: Actin; Cytokinesis; Cytoskeleton; Polypyridyl Complexes; Ruthenium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton
  • Actins / metabolism
  • Cytokinesis*
  • Endosomal Sorting Complexes Required for Transport / metabolism
  • Molecular Docking Simulation
  • Ruthenium* / metabolism
  • Ruthenium* / pharmacology

Substances

  • Actins
  • Endosomal Sorting Complexes Required for Transport
  • Ruthenium