Publication details

Dishevelled is a NEK2 kinase substrate controlling dynamics of centrosomal linker proteins

Authors

ČERVENKA Igor VALNOHOVÁ Jana BERNATÍK Ondřej HARNOŠ Jakub RÁDSETOULAL Matěj ŠEDOVÁ Kateřina HANÁKOVÁ Kateřina POTĚŠIL David SEDLÁČKOVÁ Miroslava SALAŠOVÁ Alena STEINHART Zachary ANGERS Stephane SCHULTE Gunnar HAMPL Aleš ZDRÁHAL Zbyněk BRYJA Vítězslav

Year of publication 2016
Type Article in Periodical
Magazine / Source Proceedings of the National Academy of Sciences of the United States of America
MU Faculty or unit

Faculty of Science

Citation
Doi http://dx.doi.org/10.1073/pnas.1608783113
Field Genetics and molecular biology
Keywords Wnt signaling; centrosome; Dishevelled; NEK2; linker proteins
Attached files
Description Dishevelled (DVL) is a key scaffolding protein and a branching point in Wnt signaling pathways. Here, we present conclusive evidence that DVL regulates the centrosomal cycle. We demonstrate that DVL dishevelled and axin (DIX) domain, but not DIX domain-mediated multimerization, is essential for DVL's centrosomal localization. DVL accumulates during the cell cycle and associates with NIMA-related kinase 2 (NEK2), which is able to phosphorylate DVL at amultitude of residues, as detected by a set of novel phospho-specific antibodies. This creates interfaces for efficient binding to CDK5 regulatory subunit-associated protein 2 (CDK5RAP2) and centrosomal Nek2-associated protein 1 (C-NAP1), two proteins of the centrosomal linker. Displacement of DVL from the centrosome and its release into the cytoplasm on NEK2 phosphorylation is coupled to the removal of linker proteins, an event necessary for centrosomal separation and proper formation of the mitotic spindle. Lack of DVL prevents NEK2-controlled dissolution of loose centrosomal linker and subsequent centrosomal separation. Increased DVL levels, in contrast, sequester centrosomal NEK2 and mimic monopolar spindle defects induced by a dominant negative version of this kinase. Our study thus uncovers molecular crosstalk between centrosome and Wnt signaling.
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