Lookup NU author(s): Dr Diana Papini,
Professor Jonathan Higgins
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
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.
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
Online publication date: 09/07/2015
Acceptance date: 29/05/2015
Date deposited: 12/06/2015
ISSN (electronic): 2041-1723
Publisher: Nature Publishing Group
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