PUBLICATION
Centrobin controls primary ciliogenesis in vertebrates
- Authors
- Ogungbenro, Y.A., Tena, T.C., Gaboriau, D., Lalor, P., Dockery, P., Philipp, M., Morrison, C.G.
- ID
- ZDB-PUB-180223-1
- Date
- 2018
- Source
- The Journal of cell biology 217(4): 1205-1215 (Journal)
- Registered Authors
- Philipp, Melanie
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Cell Cycle Proteins/genetics
- Cell Cycle Proteins/metabolism*
- Centrioles/metabolism*
- Centrioles/ultrastructure
- Cilia/metabolism*
- Cilia/ultrastructure
- Epithelial Cells/metabolism*
- Epithelial Cells/ultrastructure
- Gene Expression Regulation
- HCT116 Cells
- Humans
- Microcephaly/genetics
- Microcephaly/metabolism
- Microtubule-Associated Proteins/metabolism
- Phosphoproteins/metabolism
- Protein Binding
- Protein Interaction Domains and Motifs
- Retinal Pigment Epithelium/metabolism*
- Retinal Pigment Epithelium/ultrastructure
- Signal Transduction
- Telomerase/genetics
- Telomerase/metabolism
- Tubulin/metabolism
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 29440264 Full text @ J. Cell Biol.
Citation
Ogungbenro, Y.A., Tena, T.C., Gaboriau, D., Lalor, P., Dockery, P., Philipp, M., Morrison, C.G. (2018) Centrobin controls primary ciliogenesis in vertebrates. The Journal of cell biology. 217(4):1205-1215.
Abstract
The BRCA2 interactor, centrobin, is a centrosomal protein that has been implicated in centriole duplication and microtubule stability. We used genome editing to ablate CNTROB in hTERT-RPE1 cells and observed an increased frequency of monocentriolar and acentriolar cells. Using a novel monoclonal antibody, we found that centrobin primarily localizes to daughter centrioles but also associates with mother centrioles upon serum starvation. Strikingly, centrobin loss abrogated primary ciliation upon serum starvation. Ultrastructural analysis of centrobin nulls revealed defective axonemal extension after mother centriole docking. Ciliogenesis required a C-terminal portion of centrobin that interacts with CP110 and tubulin. We also depleted centrobin in zebrafish embryos to explore its roles in an entire organism. Centrobin-depleted embryos showed microcephaly, with curved and shorter bodies, along with marked defects in laterality control, morphological features that indicate ciliary dysfunction. Our data identify new roles for centrobin as a positive regulator of vertebrate ciliogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping