Midbody localization of vinexin recruits rhotekin to facilitate cytokinetic abscission

Cell Cycle. 2017;16(21):2046-2057. doi: 10.1080/15384101.2017.1284713. Epub 2017 Sep 29.

Abstract

Vinexin is a SH3 domain-containing adaptor protein that has diverse roles in cell adhesion, signal transduction, gene regulation and stress granule assembly. In this study, we found that vinexin localizes at the midbody during cell division and facilitates cytokinesis. Knockdown of vinexin in HeLa cells delayed the mitotic cell cycle progression and increased the time of cell abscission and the failure to resolve the cytoplasmic bridge. Midbody-localized vinexin is essential for recruiting rhotekin to this structure for cytokinesis because overexpression of a vinexin mutant without a rhotekin-binding motif or knockdown of rhotekin also impaired cytokinetic abscission and increased the number of cells arrested at the midbody stage. Aberrant expression of vinexin and rhotekin in various cancers has been implicated to promote metastasis because of their functions in cell adhesion and signaling. Our findings reveal a novel role of vinexin and rhotekin in cytokinetic abscission and provide another perspective of how both molecules may affect oncogenic transformation via this fundamental cell cycle process.

Keywords: cell abscission; cytokinesis; midbody; rhotekin; vinexin.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Apoptosis Regulatory Proteins
  • Cell Cycle / physiology
  • Cell Cycle Proteins / metabolism
  • Cell Division / physiology
  • Cytokinesis / physiology*
  • GTP-Binding Proteins
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Muscle Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • Muscle Proteins
  • RTKN protein, human
  • SORBS3 protein, human
  • GTP-Binding Proteins