Pharmaceutical Sciences Faculty Publications

Identification of a Novel Wnt5a-CK1ɛ-Dvl2-Plk1-Mediated Primary Cilia Disassembly Pathway

Document Type

Article

Publication Date

5-18-2012

Journal Title

The EMBO Journal

ISSN

1460-2075

Volume

31

Issue

14

First Page

3104

Last Page

3117

DOI

10.1038/emboj.2012.144

PubMed ID

22609948

PubMed Central® ID

PMC3400010

Abstract

Non-motile primary cilium is an antenna-like structure whose defect is associated with a wide range of pathologies, including developmental disorders and cancer. Although mechanisms regulating cilia assembly have been extensively studied, how cilia disassembly is regulated remains poorly understood. Here, we report unexpected roles of Dishevelled 2 (Dvl2) and interphase polo-like kinase 1 (Plk1) in primary cilia disassembly. We demonstrated that Dvl2 is phosphorylated at S143 and T224 in a manner that requires both non-canonical Wnt5a ligand and casein kinase 1 epsilon (CK1ɛ), and that this event is critical to interact with Plk1 in early stages of the cell cycle. The resulting Dvl2-Plk1 complex mediated Wnt5a-CK1ɛ-Dvl2-dependent primary cilia disassembly by stabilizing the HEF1 scaffold and activating its associated Aurora-A (AurA), a kinase crucially required for primary cilia disassembly. Thus, via the formation of the Dvl2-Plk1 complex, Plk1 plays an unanticipated role in primary cilia disassembly by linking Wnt5a-induced biochemical steps to HEF1/AurA-dependent cilia disassembly. This study may provide new insights into the mechanism underlying ciliary disassembly processes and various cilia-related disorders.

Keywords

Adaptor roteins, signal transducing, cell cycle proteins, cilia, multienzyme complexes, phosphoproteins, roto-oncogene proteins, Wnt proteins, Wnt-5a protein

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