The lhfpl5 ohnologs lhfpl5a and lhfpl5b are required for mechanotransduction in distinct populations of sensory hair cells in zebrafish.
2019
Hair cellssense and transmit auditory, vestibular, and hydrodynamic information by converting mechanical stimuli into electrical signals. This process of mechano-electrical transduction (MET) requires a mechanically-gated channel localized in the apical
stereociliaof
hair cells. In mice,
lipomaHMGIC fusion partner-like 5 (LHFPL5) acts as an auxiliary subunit of the MET channel whose primary role is to correctly localize
PCDH15and TMC1 to the
mechanotransductioncomplex. Zebrafish have two lhfpl5 genes (lhfpl5a and lhfpl5b), but their individual contributions to MET channel assembly and function have not been analyzed. Here we show that the zebrafish lhfpl5 genes are expressed in discrete populations of
hair cells: lhfpl5a expression is restricted to auditory and vestibular
hair cellsin the
inner ear, while lhfpl5b expression is specific to
hair cellsof the
lateral lineorgan. Consequently, lhfpl5a mutants exhibit defects in auditory and vestibular function, while disruption of lhfpl5b affects
hair cellsonly in the
lateral lineneuromasts. In contrast to previous reports in mice, localization of Tmc1 does not depend upon Lhfpl5 function in either the
inner earor
lateral lineorgan. In both lhfpl5a and lhfpl5b mutants, GFP-tagged Tmc1 and Tmc2b proteins still localize to the
stereociliaof
hair cells. Using a stably integrated GFP-Lhfpl5a transgene, we show that the
tip linkcadherins Pcdh15a and
Cdh23, along with the Myo7aa
motor protein, are required for correct Lhfpl5a localization at the tips of
stereocilia. Our work corroborates the evolutionarily conserved co-dependence between Lhfpl5 and
Pcdh15, but also reveals novel requirements for
Cdh23and Myo7aa to correctly localize Lhfpl5a. In addition, our data suggest that targeting of Tmc1 and Tmc2b proteins to
stereociliain zebrafish
hair cellsoccurs independently of Lhfpl5 proteins.
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