ABL1 regulates spindle orientation in adherent cells and mammalian skin.

Abstract:

: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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Matsumura S,Hamasaki M,Yamamoto T,Ebisuya M,Sato M,Nishida E,Toyoshima F

doi

10.1038/ncomms1634

subject

Has Abstract

pub_date

2012-01-17 00:00:00

pages

626

issn

2041-1723

pii

ncomms1634

journal_volume

3

pub_type

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