Search This Site

Myosin VIIa isoforms are differentially expressed in cochlear hair cells and generate tension on the mechanotransduction complex

Presenters Name: 
Jeewoo Kim
Co Presenters Name: 
Primary Research Mentor: 
Jung-Bum Shin
Secondary Research Mentor: 
Sihan Li
9:30 - 10:15
Time of Presentation: 
2019 - 9:30am to 10:15am
Newcomb Hall Ballroom
Presentation Type: 
Presentations Academic Category: 
Grant Program Recipient: 
Double Hoo Research Grant

Myosin VIIA (MYO7A) mutations are the most common cause for Usher syndrome type 1, causing deafness and blindness. Myosin VIIA has been proposed to function as a molecular motor that establishes tension on the hair cell mechanotransduction (MET) complex, but without conclusive evidence. We report that the mouse cochlea expresses two MYO7A isoforms, generated by alternative transcription start sites. Using HA and Myc tags on the long and short isoform, respectively, we visualized the subcellular localization of Myo7a to the upper tip link densities. We also genetically modified mice in which the longer isoform (MYO7A-L) is specifically deleted (Myo7a-ΔL mouse). MYO7A expression considerably decreased in inner hair cells (IHCs), but its expression was only mildly affected in outer hair cells (OHCs), suggesting that MYO7A-L is preferentially expressed in IHCs, while the shorter isoform (MYO7A-S) is predominantly expressed in OHCs. Despite the MYO7A reduction in IHCs, the hair cells still develop normally, and auditory brainstem response thresholds indicate mildly affected hearing initially which worsens overtime. Electrophysiological analysis of MET currents demonstrated that mutant IHCs have normal peak currents, but exhibit markedly reduced resting open probability and a slower current onset, consistent with a role of MYO7A in establishing tip-link tension. Mirroring the gradual decline in MET and hearing function, the transducing rows of IHC stereocilia degenerate over time as well. Taken together, we provide evidence for a distinct expression of MYO7A isoforms in IHCs and OHCs, with potential implications for MYO7A’s role in specifying MET of hair cell subtypes.