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Multiple PDZ Domain Protein Maintains Patterning of the Apical Cytoskeleton in Sensory Hair Cells

View ORCID ProfileAmandine Jarysta, View ORCID ProfileBasile Tarchini
doi: https://doi.org/10.1101/2021.02.20.432099
Amandine Jarysta
1The Jackson Laboratory, Bar Harbor, ME, 04609, USA
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Basile Tarchini
1The Jackson Laboratory, Bar Harbor, ME, 04609, USA
2Department of Medicine, Tufts University, Boston, 02111, MA, USA
3Graduate School of Biomedical Science and Engineering (GSBSE), University of Maine, Orono, 04469, ME, USA
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  • For correspondence: basile.tarchini@jax.org
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SUMMARY

Sound transduction occurs in the hair bundle, the apical compartment of sensory hair cells in the inner ear. The hair bundle is formed of stereocilia aligned in rows of graded heights. It was previously shown that the GNAI-GPSM2 complex is part of a developmental blueprint that defines the polarized organization of the apical cytoskeleton in hair cells, including stereocilia distribution and elongation. Here we report a novel and critical role for Multiple PDZ domain (MPDZ) protein during apical hair cell morphogenesis. We show that MPDZ is enriched at the hair cell apical membrane, and required there to maintain the proper segregation of apical blueprints proteins, including GNAI-GPSM2. Loss of the blueprint coincides with misaligned stereocilia in Mpdz mutants, and results in permanently misshapen hair bundles. Graded molecular and structural defects along the cochlea can explain the profile of hearing loss in Mpdz mutants, where deficits are most severe at high frequencies.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 22, 2021.
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Multiple PDZ Domain Protein Maintains Patterning of the Apical Cytoskeleton in Sensory Hair Cells
Amandine Jarysta, Basile Tarchini
bioRxiv 2021.02.20.432099; doi: https://doi.org/10.1101/2021.02.20.432099
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Multiple PDZ Domain Protein Maintains Patterning of the Apical Cytoskeleton in Sensory Hair Cells
Amandine Jarysta, Basile Tarchini
bioRxiv 2021.02.20.432099; doi: https://doi.org/10.1101/2021.02.20.432099

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