PUBLICATION
Clarin-1 acts as a modulator of mechanotransduction activity and presynaptic ribbon assembly
- Authors
- Ogun, O., Zallocchi, M.
- ID
- ZDB-PUB-141105-6
- Date
- 2014
- Source
- The Journal of cell biology 207(3): 375-391 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Cadherins/metabolism
- Cilia/metabolism
- Cilia/ultrastructure
- Endocytosis
- Hair Cells, Auditory/physiology*
- HeLa Cells
- Humans
- Mechanotransduction, Cellular*
- Membrane Proteins/physiology*
- Presynaptic Terminals/metabolism*
- Protein Transport
- Secretory Vesicles/metabolism
- Usher Syndromes/genetics
- Zebrafish
- Zebrafish Proteins/metabolism
- Zebrafish Proteins/physiology*
- PubMed
- 25365995 Full text @ J. Cell Biol.
Citation
Ogun, O., Zallocchi, M. (2014) Clarin-1 acts as a modulator of mechanotransduction activity and presynaptic ribbon assembly. The Journal of cell biology. 207(3):375-391.
Abstract
Clarin-1 is a four-transmembrane protein expressed by hair cells and photoreceptors. Mutations in its corresponding gene are associated with Usher syndrome type 3, characterized by late-onset and progressive hearing and vision loss in humans. Mice carrying mutations in the clarin-1 gene have hair bundle dysmorphology and a delay in synapse maturation. In this paper, we examined the expression and function of clarin-1 in zebrafish hair cells. We observed protein expression as early as 1 d postfertilization. Knockdown of clarin-1 resulted in inhibition of FM1-43 incorporation, shortening of the kinocilia, and mislocalization of ribeye b clusters. These phenotypes were fully prevented by co-injection with clarin-1 transcript, requiring its C-terminal tail. We also observed an in vivo interaction between clarin-1 and Pcdh15a. Altogether, our results suggest that clarin-1 is functionally important for mechanotransduction channel activity and for proper localization of synaptic components, establishing a critical role for clarin-1 at the apical and basal poles of hair cells.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping