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TD-60 links RalA GTPase function to the CPC in mitosis

Lookup NU author(s): Dr Diana PapiniORCiD, Professor Jonathan HigginsORCiD

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Abstract

TD-60 (also known as RCC2) is a highly conserved protein that structurally resembles the Ran guanine exchange factor (GEF) RCC1, but has not previously been shown to have GEF activity. TD-60 has a typical Chromosomal Passenger Complex (CPC) distribution in mitotic cells, but associates with integrin complexes and is involved in cell motility during interphase. Here we show that TD-60 exhibits GEF activity, in vitro and in cells, for the small GTPase RalA. TD-60 or RalA depletion causes spindle abnormalities in prometaphase associated with abnormal centromeric accumulation of CPC components. TD-60 and RalA apparently work together to contribute to the regulation of kinetochore-microtubule interactions in early mitosis. Importantly, several mitotic phenotypes caused by TD-60 depletion are reverted by expression of a GTP-locked mutant, RalA (Q72L). The demonstration that a small GTPase participates in the regulation of the CPC reveals a level of mitotic regulation not suspected in previous studies.

Publication metadata

Author(s): Papini D, Langemeyer L, Abad MA, Kerr A, Samejima I, Eyers PA, Jeyaprakash AA, Higgins JMG, Barr FA, Earnshaw WC

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2015

Volume: 6

Online publication date: 09/07/2015

Acceptance date: 29/05/2015

Date deposited: 12/06/2015

ISSN (electronic): 2041-1723

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ncomms8678

DOI: 10.1038/ncomms8678

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