PUBLICATION
The MST1/2-SAV1 complex of the Hippo pathway promotes ciliogenesis
- Authors
- Kim, M., Kim, M., Lee, M.S., Kim, C.H., Lim, D.S.
- ID
- ZDB-PUB-141105-4
- Date
- 2014
- Source
- Nature communications 5: 5370 (Journal)
- Registered Authors
- Kim, Cheol-Hee, Lee, Mi-Sun
- Keywords
- Ciliogenesis, HIPPO signalling
- MeSH Terms
-
- Adaptor Proteins, Signal Transducing/metabolism
- Animals
- Aurora Kinase A/metabolism
- Cell Cycle Proteins/metabolism*
- Cilia/physiology*
- HEK293 Cells
- Histone Deacetylases/metabolism
- Humans
- Membrane Proteins/metabolism
- Phenotype
- Phosphoproteins/metabolism
- Protein Serine-Threonine Kinases/metabolism*
- Tumor Suppressor Proteins/metabolism
- Zebrafish
- PubMed
- 25367221 Full text @ Nat. Commun.
Citation
Kim, M., Kim, M., Lee, M.S., Kim, C.H., Lim, D.S. (2014) The MST1/2-SAV1 complex of the Hippo pathway promotes ciliogenesis. Nature communications. 5:5370.
Abstract
Primary cilia are microtubule-based organelles that protrude from polarized epithelial cells. Although many structural and trafficking molecules that regulate ciliogenesis have been discovered, signalling proteins are not well defined. Here we show that the MST1/2-SAV1 complex, a core component of the Hippo pathway, promotes ciliogenesis. MST1 is activated during ciliogenesis and localizes to the basal body of cilia. Depletion of MST1/2 or SAV1 impairs ciliogenesis in cultured cells and induces ciliopathy phenotypes in zebrafish. MST1/2-SAV1 regulates ciliogenesis through two independent mechanisms: MST1/2 binds and phosphorylates Aurora kinase A (AURKA), leading to dissociation of the AURKA/HDAC6 cilia-disassembly complex; and MST1/2-SAV1 associates with the NPHP transition-zone complex, promoting ciliary localization of multiple ciliary cargoes. Our results suggest that components of the Hippo pathway contribute to establish a polarized cell structure in addition to regulating proliferation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping