Two NEMO-like Ubiquitin-Binding Domains in CEP55 Differently Regulate Cytokinesis
Résumé
(F.A.) HIGHLIGHTS CEP55 contains two NEMO-like NOA and UBZ domains CEP55 NOA and UBZ are crucial for the CEP55 function in cytokinetic coordination UBZ CEP55 functions as cargo receptor to the midbody in a ubiquitin-dependent manner UBZ CEP55 preferentially binds non-degradative linear and K63 polyubiquitin chains Said Halidi et al., iScience 20, SUMMARY CEP55 regulates the final critical step of cell division termed cytokinetic abscission. We report herein that CEP55 contains two NEMO-like ubiquitin-binding domains (UBDs), NOA and ZF, which regulate its function in a different manner. In vitro studies of isolated domains showed that NOA adopts a dimeric coiled-coil structure, whereas ZF is based on a UBZ scaffold. Strikingly, CEP55 knocked-down HeLa cells reconstituted with the full-length CEP55 ubiquitin-binding defective mutants, containing structure-guided mutations either in NOA CEP55 or ZF CEP55 domains, display severe abscission defects. In addition, the ZF CEP55 can be functionally replaced by some ZF-based UBDs belonging to the UBZ family, indicating that the essential function of ZF CEP55 is to act as ubiquitin receptor. Our work reveals an unexpected role of CEP55 in non-degradative ubiquitin signaling during cytokinetic abscis-sion and provides a molecular basis as to how CEP55 mutations can lead to neurological disorders such as the MARCH syndrome.
Origine : Publication financée par une institution
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