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

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 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 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 blueprints 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.

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

SUMMARYSound 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.

Laser-sound: optoacoustic transduction from digital audio streams

This work presents a novel laser-based optoacoustic transducer capable of reproducing controlled and continuous sound of arbitrary complexity in the air or on solid targets. Light-to-sound transduction is achieved via laser-induced breakdown, leading to the formation of plasma acoustic sources in any desired spatial location. The acoustic signal is encoded into pulse streams via a discrete-time audio modulation and is reproduced by fast consecutive excitation of the target medium with appropriately modulated laser pulses. This results in the signal being directly reconstructed at the desired location of the target medium without the need for a receiver or demodulation device. In this work, the principles and evaluation results of such a novel laser-sound prototype system are presented. The performance of the prototype is evaluated by systematic experimental measurements of audio test signals, from which the basic acoustical response is derived. Moreover, a generic computational model is presented that allows for the simulation of laser-sound reproduction of 1-bit or multibit audio streams. The model evaluations are validated by comparison with the acoustic measurements, whereby a good agreement is found. Finally, the computational model is used to simulate an ideal optoacoustic transducer based on the specifications of state-of-the-art commercially available lasers.

Cochlear amplification and tuning depend on the cellular arrangement within the organ of Corti

The field of cochlear mechanics has been undergoing a revolution due to recent findings made possible by advancements in measurement techniques. While it has long been assumed that basilar-membrane (BM) motion is the most important determinant of sound transduction by the inner hair cells (IHCs), it turns out that other parts of the sensory epithelium closer to the IHCs, such as the reticular lamina (RL), move with significantly greater amplitude for weaker sounds. It has not been established how these findings are related to the complex cytoarchitecture of the organ of Corti between the BM and RL, which is composed of a lattice of asymmetric Y-shaped elements, each consisting of a basally slanted outer hair cell (OHC), an apically slanted phalangeal process (PhP), and a supporting Deiters’ cell (DC). Here, a computational model of the mouse cochlea supports the hypothesis that the OHC micromotors require this Y-shaped geometry for their contribution to the exquisite sensitivity and frequency selectivity of the mammalian cochlea. By varying only the OHC gain parameter, the model can reproduce measurements of BM and RL gain and tuning for a variety of input sound levels. Malformations such as reversing the orientations of the OHCs and PhPs or removing the PhPs altogether greatly reduce the effectiveness of the OHC motors. These results imply that the DCs and PhPs must be properly accounted for in emerging OHC regeneration therapies.