PUBLICATION
Integrin α8 and Pcdh15 act as a complex to regulate cilia biogenesis in sensory cells
- Authors
- Goodman, L., Zallocchi, M.
- ID
- ZDB-PUB-171103-15
- Date
- 2017
- Source
- Journal of Cell Science 130: 3698-3712 (Journal)
- Registered Authors
- Keywords
- Integrin α8, Pcdh15, Sensory cilia, Usher syndrome
- MeSH Terms
-
- Actin Cytoskeleton/metabolism
- Actin Cytoskeleton/ultrastructure
- Animals
- Cadherins/antagonists & inhibitors
- Cadherins/deficiency
- Cadherins/genetics*
- Centrioles/metabolism
- Centrioles/ultrastructure
- Cilia/metabolism*
- Cilia/ultrastructure
- Disease Models, Animal
- Endocytosis
- Gene Expression Regulation, Developmental
- Hair Cells, Auditory/metabolism*
- Hair Cells, Auditory/ultrastructure
- Humans
- Integrins/antagonists & inhibitors
- Integrins/deficiency
- Integrins/genetics*
- Larva/genetics
- Larva/growth & development
- Larva/metabolism
- Monomeric GTP-Binding Proteins/genetics
- Monomeric GTP-Binding Proteins/metabolism
- Mutation
- Protein Binding
- RNA, Small Interfering/genetics
- RNA, Small Interfering/metabolism
- Signal Transduction
- Usher Syndromes/genetics
- Usher Syndromes/metabolism
- Usher Syndromes/pathology
- Zebrafish/genetics*
- Zebrafish/growth & development
- Zebrafish/metabolism
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/deficiency
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- rab GTP-Binding Proteins/genetics
- rab GTP-Binding Proteins/metabolism
- PubMed
- 28883094 Full text @ J. Cell Sci.
Citation
Goodman, L., Zallocchi, M. (2017) Integrin α8 and Pcdh15 act as a complex to regulate cilia biogenesis in sensory cells. Journal of Cell Science. 130:3698-3712.
Abstract
The way an organism perceives its surroundings depends on sensory systems and the highly specialized cilia present in the neurosensory cells. Here, we describe the existence of an integrin α8 (Itga8) and protocadherin-15a (Pcdh15a) ciliary complex in neuromast hair cells in a zebrafish model. Depletion of the complex via downregulation or loss-of-function mutation leads to a dysregulation of cilia biogenesis and endocytosis. At the molecular level, removal of the complex blocks the access of Rab8a into the cilia as well as normal recruitment of ciliary cargo by centriolar satellites. These defects can be reversed by the introduction of a constitutively active form of Rhoa, suggesting that Itga8-Pcdh15a complex mediates its effect through the activation of this small GTPase and probably by the regulation of actin cytoskeleton dynamics. Our data points to a novel mechanism involved in the regulation of sensory cilia development, with the corresponding implications for normal sensory function.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping