The lhfpl5 Ohnologs lhfpl5a and lhfpl5b Are Required for Mechanotransduction in Distinct Populations of Sensory Hair Cells in Zebrafish

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Timothy,Pacentine,Itallia V,Venuto,Alexandra,Clemens,Rachel,Nicolson,Teresa Erickson (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Hair cells sense and transmit auditory, vestibular, and hydrodynamic information byconverting mechanical stimuli into electrical signals. This process of mechano-electricaltransduction (MET) requires a mechanically gated channel localized in the apicalstereocilia of hair cells. In mice, lipoma HMGIC fusion partner-like 5 (LHFPL5) actsas an auxiliary subunit of the MET channel whose primary role is to correctly localizePCDH15 and TMC1 to the mechanotransduction complex. Zebrafish have two lhfpl5genes (lhfpl5a and lhfpl5b), but their individual contributions to MET channel assemblyand function have not been analyzed. Here we show that the zebrafish lhfpl5 genesare expressed in discrete populations of hair cells: lhfpl5a expression is restricted toauditory and vestibular hair cells in the inner ear, while lhfpl5b expression is specificto hair cells of the lateral line organ. Consequently, lhfpl5a mutants exhibit defects inauditory and vestibular function, while disruption of lhfpl5b affects hair cells only in thelateral line neuromasts. In contrast to previous reports in mice, localization of Tmc1does not depend upon Lhfpl5 function in either the inner ear or lateral line organ. Inboth lhfpl5a and lhfpl5b mutants, GFP-tagged Tmc1 and Tmc2b proteins still localizeto the stereocilia of hair cells. Using a stably integrated GFP-Lhfpl5a transgene, weshow that the tip link cadherins Pcdh15a and Cdh23, along with the Myo7aa motorprotein, are required for correct Lhfpl5a localization at the tips of stereocilia. Our workcorroborates the evolutionarily conserved co-dependence between Lhfpl5 and Pcdh15,but also reveals novel requirements for Cdh23 and Myo7aa to correctly localize Lhfpl5a.In addition, our data suggest that targeting of Tmc1 and Tmc2b proteins to stereociliain zebrafish hair cells occurs independently of Lhfpl5 proteins.

Additional Information

Publication

Other

Language: English

Date: 2020

Keywords

hair cell, mechanotransduction, deafness, lateral line, zebrafish, LHFPL5, TMC1, PCDH15

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