新学術領域研究
「ミクロからマクロへ階層を超える秩序形成」
テクニカルセミナー
日時： 11 月 28 日（金） 17:30-18:30
演者： 前田 礼男 博士
Postdoctoral Researcher, Teresa Nicolson laboratory,
Oregon Health & Science University
演題：
Exploring the roles of Protocadherin 15 (Pcdh15)
and Transmembrane channel-like proteins (Tmcs)
in mechanotransduction of zebrafish hair cells
Hair cells are specialized sensory receptor cells of both the auditory system and the vestibular
system in vertebrates. The common feature of hair cells is the hair bundle, which is the sensory
organelle formed by the ordered staircase-like structure of stereocilia. Mechanical deflection of a
hair bundle increases the tension of tip links that interconnect the stereocilia, and converts
mechanical force into a neural signal. These tip links are thought to pull open the force-gated
transduction channels, resulting in the influx of cations. To date, the identity of the mechanosensitive
channels in the stereocilia is still unknown, although several candidate proteins have been proposed.
The zebrafish is a powerful model organism for studying the molecular basis of inner ear
development and function. Previous studies in zebrafish have helped to elucidate the genes
required for function of hair cells, including Pcdh15a. Moreover, recent studies in mammals
suggest that PCDH15a is a central component of tip links and may be closely associated with the
mechanotransduction channel. Here we sought to identify the proteins that interact with zebrafish
Pcdh15a to determine how the tip link is coupled to the transduction complex. Using a membranebased yeast two-hybrid screen, we identified an N-terminal fragment of Transmembrane channel-like
2a (Tmc2a). Tmc2a is an orthologue of mammalian TMC2. Recent studies reported that TMC1
and TMC2 are components of the mechanotransduction channel in mammalian hair cells. To
investigate the roles of zebrafish Tmc2a in hair cells, we overexpressed N-terminal fragments of
Tmc2a in hair cells to interfere with the association between Pcdh15a and Tmc2a. Upon
overexpression, we detected mislocalization of Pcdh15a in hair bundles and significant decreases in
responses to mechanical stimuli. These results suggest that the interaction between Pcdh15a and
Tmc2a is critical for mechanotransduction in zebrafish hair cells. Taken together with previous
studies in mammals, our data support the idea that TMC1 and TMC2 are key components of the
mechanotransduction complex in auditory/vestibular hair cells.
In this seminar, I will present recent progress and discuss the key findings in understanding the
molecular mechanisms of mechanotransduction of hair cells in vertebrates.
参考文献
Maeda R, Kindt KS, Mo W, et al. (2014) Tip-link protein protocadherin 15 interacts with
transmembrane channel-like proteins TMC1 and TMC2. Proc Natl Acad Sci USA.
vol.111, 12907-12912
場所： 東京大学理学部２号館 201 号室
お問い合わせ：武田洋幸（東大・院理・生科、03-5841-4431）