Multiple PDZ domain protein maintains patterning of the apical cytoskeleton in sensory hair cells.

Document Type

Article

Publication Date

7-15-2021

Publication Title

Development (Cambridge, England)

Keywords

JMG

JAX Source

Development 2021 Jul 15; 148(14):dev199549

Volume

148

Issue

14

ISSN

1477-9129

PMID

34228789

DOI

https://doi.org/10.1242/dev.199549

Grant

DC015242, DC018304, A.J. was supported by a 2-year postdoctoral fellowship from Fondation pour l’Audition (FPA RD2018-3).

Abstract

Sound transduction occurs in the hair bundle, the apical compartment of sensory hair cells in the inner ear. The hair bundle is formed of actin-based 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 role for multiple PDZ domain (MPDZ) protein during apical hair cell morphogenesis in mouse. We show that MPDZ is enriched at the hair cell apical membrane along with MAGUK p55 subfamily member 5 (MPP5/PALS1) and the Crumbs protein CRB3. MPDZ is required there to maintain the proper segregation of apical blueprint proteins, including GNAI-GPSM2. Loss of the blueprint coincides with misaligned stereocilia placement in Mpdz mutant hair cells, 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.

Comments

The Mpdz mouse model was produced by the KOMP program led by Steve Murray at The Jackson Laboratory, and was shared by the group of Patsy Nishina.

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