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

The dinuclear Ru(II) 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 bi...

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Detalles Bibliográficos
Autores principales: Gill, Martin R., Jarman, Paul J., Hearnden, Vanessa, Fairbanks, Simon D, Bassetto, Marcella, Maib, Hannes, Palmer, John, Ayscough, Kathryn R., Thomas, Jim A., Smythe, Carl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Communications
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9323417/
https://www.ncbi.nlm.nih.gov/pubmed/35416386
http://dx.doi.org/10.1002/anie.202117449
Descripción
Sumario:The dinuclear Ru(II) 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.

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