Ion channels: Hearing aid
Nature 424, 28 - 29 (03 July 2003); doi:10.1038/424028a
Ion channels: Hearing aid
RACHEL A. DUMONT AND PETER G. GILLESPIE
Rachel A. Dumont and Peter G. Gillespie are at the Oregon Hearing Research Center and the Vollum Institute, Oregon Health &
Science University, Portland, Oregon 97239, USA.
e-mail: gillespp@ohsu.edu
Mechanically controlled ion channels -- transduction channels -- are a key feature of the cells
that detect sound, touch and movement. In fruitfly ears, the channels belong to a very familiar
group of proteins.
Sensory information, such as that carried by light, odours and sound, continuously washes over us,
revealing the nature of the outside world. Because organisms place a premium on detecting such
signals with high specificity and sensitivity, specialized cells have evolved to capture each type of
stimulus. Mechanical stimuli are no exception, and most organisms use mechanoreceptor cells to
detect sound, touch and movement. Central to mechanoreception are ion channels located in the outer
membranes of mechanoreceptor cells; these 'transduction' channels detect mechanical stimuli and, by
modulating ion entry, control the cells' electrical excitability in proportion to the size of the stimulus.
That excitation in turn enables appropriate electrical signals to be sent to the brain. The precise
channels involved in mechanoreception have, for the most part, evaded identification, because the cells
are exceedingly scarce. However, in an exciting report on page 81 of this issue, Kim and colleagues1
show that Nanchung -- a newly discovered member of the TRP protein family -- is the transduction
channel needed for fruitflies to hear.
A fly detects courtship songs with its ear, Johnston's organ2. The molecular details of this feat are
largely unknown, however. One reason for wanting to find out is that many molecular systems in
Drosophila are closely related evolutionarily to those in higher organisms -- and so identifying the
molecules that transduce mechanical stimuli in flies should have broader significance. Advantages to
studying mechanotransduction in flies rather than more complex organisms include the ability to carry
out genetic screens.
Although several such screens have been conducted, progress in finding the molecules responsible for
touch perception and hearing has been slow3. A notable success was the discovery that flies rely on
NompC, another TRP channel, to detect movement of their sensory bristles -- small hairs that
decorate their bodies4. NompC could not, however, be the only fly transduction channel; fruitflies that
lack this protein still retain a small residual electrical response when their bristles are deflected4.
Moreover, these flies enjoy nearly normal hearing2. Additional transduction channels clearly awaited
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Ion channels: Hearing aid
discovery.
Nanchung ('Nan' for short) is one such channel: Kim et al.1 present compelling evidence that this TRP-
family member is essential for Drosophila hearing. In the absence of the nan gene, flies do not hear.
Moreover, nan is expressed by mechanoreceptor cells in Johnston's organ, particularly in the outer
dendritic segment (Fig. 1), where transduction is thought to take place. Finally, expression of nan in
tissue-culture cells leads to the appearance of a channel that is activated by one type of mechanical
stimulus, osmotic challenge. Although Nan might be working by activating another channel in these
cells, it is more likely that Kim et al. have described some of the conductance properties of the
transduction channel that is directly responsible for sound detection. TRP channels -- named after
transient receptor potential, a fly gene essential for phototransduction -- have been found to mediate
sensory transduction in a wide variety of cell types5. Nan belongs to the TRPV subfamily, which has
been implicated in sensing pain, temperature, odours, osmotic pressure and touch6. With Kim and
colleagues' findings, we can now add sound to this list.
Figure 1 Fly and vertebrate auditory mechanoreceptors. Full legend
High resolution image and legend (73k)
Fly hearing may be a valuable model system for understanding other mechanoreceptors, not least the
vertebrate inner ear's hair cell. This hypothesis has not been accepted by all, perhaps in part because of
differences in appearance between the two cell types (Fig. 1). For instance, fly mechanoreceptors such
as those in Johnston's organ rely on a single long, thin protrusion, or 'sensory process', to perceive
mechanical stimuli7. By contrast, a vertebrate hair cell carries out transduction with its hair bundle,
which is composed of some 100 clustered processes called stereocilia8. Beyond sheer numbers, these
processes differ fundamentally in their structural proteins: hair-cell stereocilia are filled with actin,
whereas the fly sensory process derives from a cilium constructed of tubulin.
Despite these anatomical differences, there are some remarkable similarities. Both types of sensory
process are bathed in an unusual fluid, endolymph, which is distinguished by a high K+ concentration
and a substantial extracellular potential7, 8. Moreover, the responses of Drosophila and vertebrate
mechanoreceptors to mechanical stimuli show striking resemblances in their speed, sensitivity and
adaptation4. Finally, vertebrate and invertebrate ears have conserved the molecules that control
development of mechanoreceptor cells8. These cells may well be derived from a common, ancient
precursor -- supporting that idea, although vertebrate hair cells rely on stereocilia for transduction,
they too have a tubulin-based cilium (the kinocilium; Fig. 1).
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Ion channels: Hearing aid
If these cells are evolutionarily linked, additional molecular similarities should emerge -- and indeed
they have. In one example, NompA, a component of the structure that caps the fly's sensory process9,
resembles the tectorins -- proteins that contribute to a similar structure in vertebrate ears (Fig. 1). In
another, NompC (found in Drosophila bristles) underlies transduction in zebrafish hair cells10.
Although mammalian genomes conspicuously lack a close relative of the nompC gene, its presence in
zebrafish nevertheless dramatically reinforces the hypothesis that the molecules responsible for
Drosophila mechanotransduction have relatives in vertebrate systems.
Could the transduction channel in mammalian hair cells -- like that in fruitfly ears1 -- belong to the
TRPV subfamily? Of the six known vertebrate TRPV proteins, a tempting candidate is TRPV4, which
is found in one class of hair cells (auditory hair cells) and can be activated osmotically when expressed
in tissue-culture cells11. To complicate the story, however, the hair-cell transduction channel may not
be made up of a single type of protein; for example, multiple TRP-channel subunits interact to achieve
correct targeting and function of sensory channels in the worm Caenorhabditis elegans12. Although
the demonstration of the role of Nan in fly hearing does not pinpoint the identity of the hair-cell
transduction channel, it does direct our gaze firmly at the TRPV subfamily.
References
1. Kim, J. et al. Nature 424, 81-84 (2003). | Article |
2. Eberl, D. F., Hardy, R. W. & Kernan, M. J. J. Neurosci. 20, 5981-5988 (2000). | PubMed | ChemPort |
3. Ernstrom, G. G. & Chalfie, M. Annu. Rev. Genet. 36, 411-453 (2002). | Article | PubMed | ChemPort |
4. Walker, R. G., Willingham, A. T. & Zuker, C. S. Science 287, 2229-2234
(2000). | Article | PubMed | ChemPort |
5. Montell, C., Birnbaumer, L. & Flockerzi, V. Cell 108, 595-598 (2002). | PubMed | ChemPort |
6. Gunthorpe, M. J., Benham, C. D., Randall, A. & Davis, J. B. Trends Pharmacol. Sci. 23, 183-191
(2002). | Article | PubMed | ChemPort |
7. Keil, T. A. Microsc. Res. Tech. 39, 506-531 (1997). | Article | PubMed | ChemPort |
8. Gillespie, P. G. & Walker, R. G. Nature 413, 194-202 (2001). | Article | PubMed | ChemPort |
9. Chung, Y. D., Zhu, J., Han, Y. & Kernan, M. J. Neuron 29, 415-428 (2001). | PubMed | ChemPort |
10. Sidi, S., Friedrich, R. W. & Nicolson, T. Science published online 12 June,
doi:10.1126/science.1084370 (2003). | PubMed |
11. Liedtke, W. et al. Cell 103, 525-535 (2000). | PubMed | ChemPort |
12. Tobin, D. et al. Neuron 35, 307-318 (2002). | PubMed | ChemPort |
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Figure 1
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Figure 1
Figure 1 Fly and vertebrate auditory mechanoreceptors. In the fly ear, pairs of mechanoreceptor cells are
stimulated when the overlying dendritic cap, in response to sound waves, moves relative to the cells (arrow). Kim
et al.1 have found that the Nan ion channel is located in the outer dendritic segment, where transduction the
detection of sound stimuli and their conversion into the electrical response of the cell is thought to take place. In
a vertebrate hair cell, the movement of the overlying tectorial membrane relative to the cell deflects stereocilia,
triggering transduction; the kinocilium helps to couple these processes. The kinocilium is present in hair cells in
all vertebrates, at least during development. Structures that are anatomically and molecularly similar between fly
ear cells and vertebrate hair cells include the dendritic cap and tectorial membrane (blue), and the outer dendritic
segment and kinocilium (green).
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