ABL1 Regulates Spindle Orientation in Adherent Cells and Mammalian Skin

Overview

Journal Nat Commun

Specialty Biology

Date 2012 Jan 19

PMID 22252550

Citations 41

Authors

Shigeru Matsumura

Mayumi Hamasaki

Takuya Yamamoto

Miki Ebisuya

Mizuho Sato

Eisuke Nishida

Fumiko Toyoshima

Affiliations

Soon will be listed here.

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.

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