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During cell division, the guanine nucleotide exchange factor (GEF) ECT2 activates RhoA in a narrow zone at the cell equator in anaphase. ECT2 consists of three BRCT domains (BRCT0, 1, and 2), a catalytic GEF, and a pleckstrin homology (PH) domain. How the conserved BRCT domains spatially and temporally control ECT2 activity remains unclear. We reveal that each BRCT domain makes distinct contributions to the ECT2 function. We find that BRCT0 contributes to, and BRCT1 is essential for, ECT2 activation in anaphase. BRCT2 integrates two functions: GEF inhibition and RACGAP1 binding, which together limit ECT2 activity to a narrow zone at the cell equator. BRCT2-dependent control of active RhoA zone dimension functions in addition to the inhibitory signal of the astral microtubules. Our analysis provides detailed mechanistic insights into how ECT2 activity is regulated and how that regulation ensures, together with other signaling pathways, successful cell division. Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Sandra Schneid, Friederike Wolff, Kristina Buchner, Nils Bertram, Seren Baygün, Pedro Barbosa, Sriyash Mangal, Esther Zanin. The BRCT domains of ECT2 have distinct functions during cytokinesis. Cell reports. 2021 Mar 02;34(9):108805

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PMID: 33657383

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