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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2011-12-05T00:00:00-05:00" class="date-display-single">December 5, 2011</span></p><div class='syndicate'><h1>Key Hearing Proteins Identified</h1><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2011/20111205-hearing.jpg?itok=_QngD152&timestamp=1433360913 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2011/20111205-hearing.jpg?itok=cnnuC0np&timestamp=1433360913 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2011/20111205-hearing.jpg?itok=6pVe8OUo&timestamp=1433360913 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2011/20111205-hearing.jpg?itok=72JT-T8s&timestamp=1433360913 1x" media="screen and (min-width: 0)" />
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2011/20111205-hearing.jpg?itok=kAWhbKnq&timestamp=1433360913" alt="Photo of a young woman cupping her hand to her ear" title="Photo of a young woman cupping her hand to her ear" />
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</div><p>Researchers have found what appear to be 2 key components of the long-sought-after mechanotransduction channel in the inner ear — the place where sound waves are transformed into the electrical signals that the brain recognizes as sound.</p>
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<p>Sensory cells in the inner ear called hair cells are crucial for transforming sound into electrical signals. Hair cells also underlie our sense of balance. Sitting atop hair cells are tiny bristly structures called stereocilia. Microscopic tethers connect the tips of shorter stereocilia to the sides of adjacent taller stereocilia. Most scientists believe that as the stereocilia move, the tethers open ion channels — tiny openings in the cell that let electrically charged molecules (ions) pass in and out. The ions rushing inside begin an electrical signal that travels to the brain.</p>
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<p>While researchers have gained many insights into mechanotransduction, the ion channels involved have remained elusive. A team of researchers led by Dr. Andrew J. Griffith of NIH's National Institute on Deafness and Other Communication Disorders (NIDCD) and Dr. Jeffrey R. Holt of Harvard Medical School decided to focus on 2 proteins. Griffith and other collaborators had previously found that mutations in the <em>TMC1</em> gene cause hereditary deafness in both humans and mice. The TMC1 protein sequence suggests that it could span the cell's outer membrane and act as a channel. Another protein, TMC2, has a similar structure. The scientists deleted both genes in mice. Their findings appeared on December 1, 2011, in the<em> Journal of Clinical Investigation.</em></p>
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<p>Mice with no functional copies of <em>TMC1</em> or <em>TMC2</em> had the classic behaviors of dizzy mice — head bobbing, neck arching, unstable gait and circling movements. They were also deaf. The <em>TMC1</em> deficient mice were deaf as well, but had no balance issues. Mice without <em>TMC2</em> had no problems with hearing or balance.</p>
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<p>The scientists examined when the <em>TMC1</em> and <em>TMC2</em> genes are expressed (turned on) in the inner ears of mice. The 2 genes were expressed from birth in hair cells in both the cochlea, which is responsible for hearing, and the vestibular organs, which are responsible for balance. When mice were a week old, <em>TMC2</em> appeared to be turned off in the cochlea but not in the vestibular organs. <em>TMC1</em> continued to be expressed in mature cochlear hair cells. Taken toghter, these findings suggest that TMC1 is essential for hearing, but TMC2 is not. For balance, however, TMC2 can substitute for TMC1.</p>
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<p>In laboratory tests, hair cells lacking functional TMC1 or TMC2 had no detectable mechanotransduction currents, even though the rest of the cells' structure and function appeared normal. By using a gene therapy technique that adds proteins back into cells, the researchers were able to restore transduction to both vestibular and cochlear hair cells. This finding suggests that it might be possible to reverse these genetic deficits.</p>
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<p>The researchers found that TMC1 and TMC2 cluster at the tips of the stereocilia, where one might expect to see proteins that play a prominent role in mechanotransduction. In future work, the scientists intend to explore how TMC1 and TMC2 interact with each other as well as with other known proteins at the stereocilia tip.</p>
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</div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="http://www.nih.gov/researchmatters/september2007/09102007hearing.htm" target="_top">Proteins Pair to Form Crucial Hearing Structure</a></li><li><a href="http://www.nih.gov/researchmatters/june2006/06302006protein.htm" target="_top">A Protein That Helps Turn Sound into Sense</a></li><li><a href="http://www.nidcd.nih.gov/health/hearing/Pages/Default.aspx" target="_top">Hearing, Ear Infections, and Deafness</a></li></ul>
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<h3 class="block__title">About NIH Research Matters</h3>
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<p><strong>Editor:</strong> Harrison Wein, Ph.D.</p>
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<p><strong>Assistant Editors:</strong> Vicki Contie and Brian Doctrow, Ph.D.</p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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<p>ISSN 2375-9593</p>
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