Linking cytoplasmic dynein and transport of Rab8 vesicles to the midbody during cytokinesis by the doublecortin domain-containing 5 protein

J Cell Sci. 2011 Dec 1;124(Pt 23):3989-4000. doi: 10.1242/jcs.085407. Epub 2011 Dec 8.

Abstract

Completion of mitosis requires microtubule-dependent transport of membranes to the midbody. Here, we identified a role in cytokinesis for doublecortin domain-containing protein 5 (DCDC5), a member of the doublecortin protein superfamily. DCDC5 is a microtubule-associated protein expressed in both specific and dynamic fashions during mitosis. We show that DCDC5 interacts with cytoplasmic dynein and Rab8 (also known as Ras-related protein Rab-8A), as well as with the Rab8 nucleotide exchange factor Rabin8 (also known as Rab-3A-interacting protein). Following DCDC5 knockdown, the durations of the metaphase to anaphase transition and cytokinesis, and the proportion of multinucleated cells increases, whereas cell viability decreases. Furthermore, knockdown of DCDC5 or addition of a dynein inhibitor impairs the entry of Golgi-complex-derived Rab8-positive vesicles to the midbody. These findings suggest that DCDC5 plays an important role in mediating dynein-dependent transport of Rab8-positive vesicles and in coordinating late cytokinesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Survival
  • Cloning, Molecular
  • Cytokinesis*
  • Cytoplasmic Dyneins / genetics
  • Cytoplasmic Dyneins / metabolism*
  • Doublecortin Domain Proteins
  • Gene Knockdown Techniques
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • HeLa Cells
  • Humans
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Mitosis
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Protein Interaction Domains and Motifs
  • RNA Interference
  • Transfection
  • Transport Vesicles / metabolism
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*

Substances

  • Doublecortin Domain Proteins
  • Membrane Transport Proteins
  • Microtubule-Associated Proteins
  • Neuropeptides
  • RAB8A protein, human
  • Cytoplasmic Dyneins
  • rab GTP-Binding Proteins