PUBLICATION
Ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of Left-Right asymmetry
- Authors
- Silva, E., Betleja, E., John, E., Spear, P., Moresco, J.J., Zhang, S., Yates, J.R., Mitchell, B.J., Mahjoub, M.R.
- ID
- ZDB-PUB-151106-10
- Date
- 2016
- Source
- Molecular biology of the cell 27(1): 48-63 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Movement/physiology
- Centrioles/metabolism
- Centrosome/metabolism
- Cilia/metabolism
- Cilia/physiology*
- Cytoskeletal Proteins/genetics
- Cytoskeletal Proteins/metabolism
- Cytoskeletal Proteins/physiology*
- Embryonic Development/physiology
- Genetic Association Studies
- HEK293 Cells
- Humans
- Mice
- Morphogenesis/physiology
- Sequence Deletion
- Xenopus
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 26538025 Full text @ Mol. Biol. Cell
Citation
Silva, E., Betleja, E., John, E., Spear, P., Moresco, J.J., Zhang, S., Yates, J.R., Mitchell, B.J., Mahjoub, M.R. (2016) Ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of Left-Right asymmetry. Molecular biology of the cell. 27(1):48-63.
Abstract
The establishment of Left-Right asymmetry in vertebrates is dependent on the sensory and motile functions of cilia during embryogenesis. Mutations in CCDC11 disrupt l-R asymmetry and cause congenital heart disease in humans, yet the molecular and cellular functions of the protein remain unknown. Here, we demonstrate that Ccdc11 is a novel component of centriolar satellites, cytoplasmic granules that serve as recruitment sites for proteins destined for the centrosome and cilium. Ccdc11 interacts with core components of satellites, and its loss disrupts the subcellular organization of satellite proteins and perturbs primary cilium assembly. Ccdc11 colocalizes with satellite proteins in human multiciliated tracheal epithelia, and its loss inhibits motile ciliogenesis. Similarly, depletion of CCDC11 in Xenopus embryos causes defective assembly and motility of cilia in multiciliated epidermal cells. To determine the role of CCDC11 during vertebrate development, we generated mutant alleles in zebrafish. Loss of CCDC11 leads to defective ciliogenesis in the pronephros and within the Kupffer's vesicle, and results in aberrant l-R axis determination. Our results highlight a critical role for Ccdc11 in the assembly and function of motile cilia, and implicate centriolar satellite-associated proteins as a new class of proteins in the pathology of l-R patterning and congenital heart disease.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping