ABL1 regulates spindle orientation in adherent cells and mammalian skin

Nat Commun. 2012 Jan 17;3:626. doi: 10.1038/ncomms1634.


Despite the growing evidence for the regulated spindle orientation in mammals, a systematic approach for identifying the responsible genes in mammalian cells has not been established. Here we perform a kinase-targeting RNAi screen in HeLa cells and identify ABL1 as a novel regulator of spindle orientation. Knockdown of ABL1 causes the cortical accumulation of Leu-Gly-Asn repeat-enriched-protein (LGN), an evolutionarily conserved regulator of spindle orientation. This results in the LGN-dependent spindle rotation and spindle misorientation. In vivo inactivation of ABL1 by a pharmacological inhibitor or by ablation of the abl1 gene causes spindle misorientation and LGN mislocalization in mouse epidermis. Furthermore, ABL1 directly phosphorylates NuMA, a binding partner of LGN, on tyrosine 1774. This phosphorylation maintains the cortical localization of NuMA during metaphase, and ensures the LGN/NuMA-dependent spindle orientation control. This study provides a novel approach to identify genes regulating spindle orientation in mammals and uncovers new signalling pathways for this mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion
  • Epidermis / metabolism
  • Gene Expression Regulation*
  • HeLa Cells
  • Humans
  • Metaphase
  • Mice
  • Mice, Knockout
  • Phosphorylation
  • Proto-Oncogene Proteins c-abl / genetics
  • Proto-Oncogene Proteins c-abl / physiology*
  • RNA Interference
  • Signal Transduction
  • Skin / metabolism*
  • Spindle Apparatus*
  • Time Factors
  • Tyrosine / chemistry


  • Tyrosine
  • Proto-Oncogene Proteins c-abl