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

Diana Papini, Lars Langemeyer, Maria A Abad, Alastair Kerr, Itaru Samejima, Patrick A Eyers, Arockia Arulanandam, Jonathan M G Higgins, Francis A Barr, William C Earnshaw

Research output: Contribution to journalArticlepeer-review

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 the 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.

Original languageEnglish
Article number7678
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 9 Jul 2015

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