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Targeting of Fzr/Cdh1 for timely activation of the APC/C at the centrosome during mitotic exit.

Published version
Peer-reviewed

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Authors

Meghini, Francesco 
Tait, Xavier 
Fujimitsu, Kazuyuki 
Yamano, Hiroyuki 

Abstract

A multi-subunit ubiquitin ligase, the anaphase-promoting complex/cyclosome (APC/C), regulates critical cellular processes including the cell cycle. To accomplish its diverse functions, APC/C activity must be precisely regulated in time and space. The interphase APC/C activator Fizzy-related (Fzr or Cdh1) is localized at centrosomes in animal cells. However, neither the mechanism of its localization nor its importance is clear. Here we identify the centrosome component Spd2 as a major partner of Fzr in Drosophila. The localization of Fzr to the centriole during interphase depends on direct interaction with Spd2. By generating Spd2 mutants unable to bind Fzr, we show that centrosomal localization of Fzr is essential for optimal APC/C activation towards its centrosomal substrate Aurora A. Finally, we show that Spd2 is also a novel APC/C(Fzr) substrate. Our study is the first to demonstrate the critical importance of distinct subcellular pools of APC/C activators in the spatiotemporal control of APC/C activity.

Description

Keywords

Animals, Aurora Kinase A, Cdh1 Proteins, Centrosome, Drosophila, Drosophila Proteins, Female, Interphase, Mitosis, Mutation, Protein Binding, Time Factors

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

7

Publisher

Springer Science and Business Media LLC
Sponsorship
Cancer Research Uk (None)
Biotechnology and Biological Sciences Research Council (BB/I013938/1)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (655297)
Cancer Research UK (Career Development Fellowship), Biotechnology and Biological Sciences Research Council (project grant), Medical Research Council (project grant), Japan Society for the Promotion of Science (Postdoctoral Fellowship for Research Abroad), European Commission (Marie Skłodowska-Curie actions individual fellowship)