Mechanotransduction of the Hair Cell by Wei Xiong & Zhigang Xu

Author:Wei Xiong & Zhigang Xu
Language: eng
Format: epub
Publisher: Springer Singapore, Singapore

Are TMC1/TMC2 the MET Channels?

As mentioned above, many lines of evidence are consistent with the hypothesis that TMC1/TMC2 are MET channels of mammalian auditory hair cells. First, TMC1 and TMC2 are expressed during the right time and at the right place. In the mouse cochlea, hair cells become mechanosensitive at P1–P3, whereas Tmc2 expression starts at P0–P2, followed by expression of Tmc1. In the mouse cochlea, Tmc1 and Tmc2 are exclusively expressed in hair cells. Within hair cells, TMC1 and TMC2 were shown to localize near the tips of shorter stereocilia, coincident with the localization of MET channels. Second, heterologously expressed TMC1/TMC2 could be co-immunoprecipitated together with the lower tip-link component PCDH15, which also localizes at the tips of shorter stereocilia. Third, Tmc1/Tmc2 double knockout completely eliminates the MET currents in mouse hair cells while leaving hair bundle and tip links unaffected.

At present the role of TMC1/TMC2 as MET channels is under hot debate [89–91]. Other proteins such as LHFPL5 and TMIE behave similarly to TMC1/TMC2: they localize at the tips of shorter stereocilia and interact with PCDH15, and their mutations lead to deafness as well as loss of MET current (discussed below). Probably the biggest challenge comes from the fact that TMC1 or TMC2 so far has not been successfully shown to serve as a channel in a heterologous expression system. Heterogeneously expressed TMC1 localizes at the ER, not on the plasma membrane [73], which hinders further examination of its potential channel activity. Heterologously expressed TMC-1, one of the two TMCs that exist in C. elegans, was reported to have sodium channel activity [92], whereas similar observation has not been reported on mammalian TMCs yet.

Download

Copyright Disclaimer:
This site does not store any files on its server. We only index and link to content provided by other sites. Please contact the content providers to delete copyright contents if any and email us, we'll remove relevant links or contents immediately.