title: Clarin-1 acts as a modulator of mechanotransduction activity and presynaptic ribbon assembly.
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.
authors.affiliation: Sensory Neuroscience Department, Boys Town National Research Hospital, Omaha, NE 68131.
authors.forename: Oluwatobi
authors.initials: O
authors.lastname: Ogun
authors.affiliation: Sensory Neuroscience Department, Boys Town National Research Hospital, Omaha, NE 68131 marisa.zallocchi@boystown.org.
authors.forename: Marisa
authors.initials: M
authors.lastname: Zallocchi
mesh_terms: D000818:Animals; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000378:metabolism; D002923:Cilia / Q000378:metabolism / Q000648:ultrastructure; D004705:Endocytosis; D006198:Hair Cells, Auditory / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D040542:Mechanotransduction, Cellular; D008565:Membrane Proteins / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism*; D021381:Protein Transport; D022142:Secretory Vesicles / Q000378:metabolism; D052245:Usher Syndromes / Q000235:genetics; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: C497421:CDHR15 protein, zebrafish; C000588831:CLRN1 protein, zebrafish; D000070585:Cadherin Related Proteins; D015820:Cadherins; D008565:Membrane Proteins; D029961:Zebrafish Proteins