ZFIN ID: ZDB-PUB-141105-6
Clarin-1 acts as a modulator of mechanotransduction activity and presynaptic ribbon assembly
Ogun, O., Zallocchi, M.
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.
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.