ScienceWeek

SENSORY BIOLOGY: ON TRANSDUCTION CHANNELS

The following points are made by R.A. Dumont and P.G. Gillespie (Nature 2003 424:28):

1) Sensory information, such as that carried by light, odors 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.

2) 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 cell electrical excitability in proportion to the size of the stimulus. That excitation in turn enables appropriate electrical signals to be sent to the brain.

3) The precise channels involved in mechanoreception have, for the most part, evaded identification, because the cells are exceedingly scarce. However, Kim et al(1) have demonstrated that Nanchung -- a newly discovered member of the TRP protein family -- is the transduction channel needed for fruit flies to hear.

4) A fly detects courtship songs with its "ear", Johnston's organ(2). 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.

5) Although several such screens have been conducted, progress in finding the molecules responsible for touch perception and hearing has been slow(3). 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 bodies(4). NompC could not, however, be the only fly transduction channel; fruit flies that lack this protein still retain a small residual electrical response when their bristles are deflected(4). Moreover, these flies enjoy nearly normal hearing(2). Additional transduction channels clearly awaited discovery.

6) 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, 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.

References (abridged):

1. Kim, J. et al. Nature 424, 81-84 (2003)

2. Eberl, D. F., Hardy, R. W. & Kernan, M. J. J. Neurosci. 20, 5981-5988 (2000)

3. Ernstrom, G. G. & Chalfie, M. Annu. Rev. Genet. 36, 411-453 (2002)

4. Walker, R. G., Willingham, A. T. & Zuker, C. S. Science 287, 2229-2234 (2000)

5. Montell, C., Birnbaumer, L. & Flockerzi, V. Cell 108, 595-598 (2002)

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MOLECULAR BASIS OF MECHANOSENSORY TRANSDUCTION

The following points are made by P.G. Gillespie and R.G. Walker (Nature 2001 413:194):

1) Mechanical forces impinge on us from all directions, transmitting valuable information about the external environment. Mechanosensory cells transduce these mechanical forces and transmit this sensory information to the brain. Hearing, touch, sense of acceleration -- each informs us about what is nearby and how we are moving relative to our surroundings. An organism detects sensory information with a variety of cells that respond to force. Although different structurally, hair cells within our ear, cutaneous mechanoreceptors of our skin, and invertebrate mechanoreceptors share many mechanistic features; whether mutual molecular mechanisms underlie these similar transduction mechanisms remains to be determined.

2) As with most sensory systems, mechanosensory cells place a premium on speed and sensitivity. A common theme is for mechanical forces to be directed to specific ion channels, which can open rapidly and amplify the signal by permitting entry of large numbers of ions. Mechanical forces can also affect intracellular events in cells -- such as gene transcription --directly through the cell surface and cytoskeleton, although such mechanisms typically are not used for rapid sensory transduction.

3) Speed requires that mechanical forces be funneled directly to transduction channels, without intervening second messengers. Sensitivity requires that the maximal amount of stimulus energy be directed to the transduction channel. A general model --borrowed from worm touch receptors(1,2) and hair cells(3) --applies to many mechanosensory transduction systems: its key feature is a transduction channel that detects deflection of an external structure relative to an internal structure, such as the cytoskeleton. Such a deflection could take the form of deformation of the skin, oscillation of a hair cell's hair bundle, or vibration of a fly's bristle. Deflection changes tension in all elements of the system, and the transduction channel responds by changing its open probability.

4) In summary: Mechanotransduction -- a cell's conversion of a mechanical stimulus into an electrical signal -- reveals vital features of an organism's environment. From hair cells and skin mechanoreceptors in vertebrates, to bristle receptors in flies and touch receptors in worms, mechanically sensitive cells are essential in the life of an organism. The scarcity of these cells and the uniqueness of their transduction mechanisms have conspired to slow molecular characterization of the ensembles that carry out mechanotransduction. But recent progress in both invertebrates and vertebrates is beginning to reveal the identities of proteins essential for transduction.(4,5)

References (abridged):

1. Chalfie, M. A molecular model for mechanosensation in Caenorhabditis elegans. Biol. Bull. 192, 125-130 (1997)

2. Tavernarakis, N. & Driscoll, M. Molecular modeling of mechanotransduction in the nematode Caenorhabditis elegans. Annu. Rev. Physiol. 59, 659-689 (1997)

3. Hudspeth, A. J. Hair-bundle mechanics and a model for mechanoelectrical transduction by hair cells. Soc. Gen. Physiol. Ser. 47, 357-370 (1992)

4. Narins, P. M. & Lewis, E. R. The vertebrate ear as an exquisite seismic sensor. J. Acoust. Soc. Am. 76, 1384-1387 (1984)

5. Sukharev, S. I., Blount, P., Martinac, B., Blattner, F. R. & Kung, C. A large-conductance mechanosensitive channel in E. coli encoded by mscL alone. Nature 368, 265-268 (1994)

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