Using powerful microscopy techniques, a research
team led by scientists at the National Institute on
Deafness and Other Communication Disorders (NIDCD),
part of the National Institutes of Health (NIH), has
pinpointed in mice the precise cellular location of
two proteins known to be important for hearing and
balance. The discovery provides additional evidence
that the proteins, TMC1 and TMC2, are part of the
channel complex that is essential for the inner ear
to process sound and the signals that are key to
balance.
The study appeared in the September 8 edition of
Cell Reports and was co-led by Bechara Kachar, M.D.,
chief of the NIDCD's Laboratory of Cell Structure
and Dynamics, and NIDCD Scientific Director Andrew
J. Griffith, M.D., Ph.D. The findings expand
knowledge of the structure of the channel, enable
scientists to further explore the mechanisms by
which it functions, and may lead to new insights
into certain hearing and balance disorders.
Hair cells, which are topped by thread-like
structures called stereocilia, are the key sensory
cells in the inner ear.
Mechanoelectrical transduction (MET) channels, which
are thought to reside at stereocilia tips, are
critical to the cells' function.
The channels detect mechanical signals from sound
vibrations or changes in our position and convert
these signals into electrical pulses that are sent
to and interpreted by the brain.
While scientists have learned a lot about how the
MET channel functions, its molecular structure
largely remains a mystery. TMC1 and TMC2 have long
been suspected to be parts of the channel complex
for several reasons. The structures of both proteins
suggest that they lay in the hair cell's membrane,
as would be expected for parts of the molecular
channel, and in the absence of the proteins, the MET
channel doesn't function normally.
In addition, the TMC1 and TMC2 genes are turned on
at the same time in development that the MET channel
becomes functional. But proving that TMC1 and TMC2
are part of the channel complex—rather than having
an indirect effect on its function—has been
challenging.
To further investigate the location of TMC 1 and
TMC2 in the MET channel, the researchers tagged
mouse hair cells with with fluorescent proteins and
observed the proteins using high-resolution confocal
microscopy. This microscopy technique enables
scientists to visualize cells in detail in three
dimensions.
The scientists found that TMC1 and TMC2 are found
along the length of developing stereocilia. As the
hair cells matured, the two proteins localized
predominantly to the stereocilia tips. The images
also showed that TMC1 and TMC2 are absent from the
tips of the tallest stereocilia, where there are no
detectable MET channels.
By uncovering the TMC1 and TMC2 localization pattern
in hair cells, this work contributes to growing
evidence that these proteins are components of the
MET channel complex, and that they may be the
pore-forming transmembrane proteins of the channel.
For more information
TMC1 and TMC2 Localize at the Site of
Mechanotransduction in Mammalian Inner Ear Hair Cell
Stereocilia.
Kurima K, Ebrahim S, Pan B, Sedlacek M, Sengupta P,
Millis BA, Cui R, Nakanishi H, Fujikawa T, Kawashima
Y, Choi BY, Monahan K, Holt JR, Griffith AJ, Kachar
B. Cell Rep. 2015 Aug 26. pii:
S2211–1247(15)00848-7.
link...
MDN |