Dynein light intermediate chains maintain spindle bipolarity by functioning in centriole cohesion

J Cell Biol. 2014 Nov 24;207(4):499-516. doi: 10.1083/jcb.201408025.

Abstract

Cytoplasmic dynein 1 (dynein) is a minus end-directed microtubule motor protein with many cellular functions, including during cell division. The role of the light intermediate chains (LICs; DYNC1LI1 and 2) within the complex is poorly understood. In this paper, we have used small interfering RNAs or morpholino oligonucleotides to deplete the LICs in human cell lines and Xenopus laevis early embryos to dissect the LICs' role in cell division. We show that although dynein lacking LICs drives microtubule gliding at normal rates, the LICs are required for the formation and maintenance of a bipolar spindle. Multipolar spindles with poles that contain single centrioles were formed in cells lacking LICs, indicating that they are needed for maintaining centrosome integrity. The formation of multipolar spindles via centrosome splitting after LIC depletion could be rescued by inhibiting Eg5. This suggests a novel role for the dynein complex, counteracted by Eg5, in the maintenance of centriole cohesion during mitosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Centrioles / physiology
  • Cytoplasmic Dyneins / genetics
  • Cytoplasmic Dyneins / metabolism*
  • Dynactin Complex
  • Female
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Kinesins / antagonists & inhibitors*
  • Kinetochores
  • Microtubule Proteins / metabolism
  • Microtubule-Associated Proteins / genetics
  • Microtubules / metabolism
  • Mitosis / physiology*
  • Molecular Sequence Data
  • RNA Interference
  • RNA, Small Interfering
  • Spindle Apparatus / genetics
  • Spindle Apparatus / pathology*
  • Xenopus laevis

Substances

  • Dynactin Complex
  • KIF11 protein, human
  • Microtubule Proteins
  • Microtubule-Associated Proteins
  • RNA, Small Interfering
  • DYNC1LI1 protein, human
  • Cytoplasmic Dyneins
  • DYNC1LI2 protein, human
  • Kinesins

Associated data

  • GENBANK/AF035812
  • GENBANK/AF078849