Dynein light chain 1 and a spindle-associated adaptor promote dynein asymmetry and spindle orientation

Author:

Dunsch Anja K.1,Hammond Dean2,Lloyd Jennifer2,Schermelleh Lothar1,Gruneberg Ulrike1,Barr Francis A.1

Affiliation:

1. Department of Biochemistry, University of Oxford, Oxford OX1 3QU, England, UK

2. Cancer Research Centre, University of Liverpool, Liverpool L3 9TA, England, UK

Abstract

The cytoplasmic dynein motor generates pulling forces to center and orient the mitotic spindle within the cell. During this positioning process, dynein oscillates from one pole of the cell cortex to the other but only accumulates at the pole farthest from the spindle. Here, we show that dynein light chain 1 (DYNLL1) is required for this asymmetric cortical localization of dynein and has a specific function defining spindle orientation. DYNLL1 interacted with a spindle-microtubule–associated adaptor formed by CHICA and HMMR via TQT motifs in CHICA. In cells depleted of CHICA or HMMR, the mitotic spindle failed to orient correctly in relation to the growth surface. Furthermore, CHICA TQT motif mutants localized to the mitotic spindle but failed to recruit DYNLL1 to spindle microtubules and did not correct the spindle orientation or dynein localization defects. These findings support a model where DYNLL1 and CHICA-HMMR form part of the regulatory system feeding back spindle position to dynein at the cell cortex.

Publisher

Rockefeller University Press

Subject

Cell Biology

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