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Scientists identify molecular cause for one form of deafness
James E.
Kloeppel, Physical Sciences Editor
217-244-1073; kloeppel@illinois.edu
Released
2/5/2007
|
CHAMPAIGN, Ill. —
Scientists exploring the physics of hearing have found an underlying
molecular cause for one form of deafness, and a conceptual connection
between deafness and the organization of liquid crystals, which
are used in flat-panel displays.
Within the cochlea of the inner ear, sound waves cause the basilar membrane
to vibrate. These vibrations stimulate hair cells, which then trigger
nerve impulses that are transmitted to the brain.
Researchers have now learned that mutations in a protein called espin
can cause floppiness in tiny bundles of protein filaments within the
hair cells, impairing the passage of vibrations and resulting in deafness.
Filamentous actin (F-actin) is a rod-like protein that provides structural
framework in living cells. F-actin is organized into bundles by espin,
a linker protein found in sensory cells, including cochlear hair cells.
Genetic mutations in espin’s F-actin binding sites are linked
to deafness in mice and humans.
“We found the structure of the bundles changes dramatically when
normal espin is replaced with espin mutants that cause deafness,”
said Gerard Wong, a professor of materials
science and engineering, of physics,
and of bioengineering at the
University of Illinois at Urbana-Champaign.
“The interior structure of the bundles changes from a rigid, hexagonal
array of uniformly twisted filaments, to a liquid crystalline arrangement
of filaments,” Wong said. “Because the new organization
causes the bundles to be more than a thousand times floppier, they cannot
respond to sound in the same way. The rigidity of these bundles is essential
for hearing.”
Wong and his co-authors – Illinois postdoctoral research associate
Kirstin Purdy and Northwestern University professor of cell and molecular
biology James R. Bartles – report their findings in a paper accepted
for publication in the journal Physical Review Letters, and posted on
its Web site.
High-resolution X-ray diffraction experiments, performed by Purdy at
the Advanced Photon Source and at the Stanford Synchrotron Radiation
Laboratory, allowed the researchers to solve the structure of various
espin-actin bundles.
“As the ability of espin to cross-link F-actin is decreased by
using genetically modified ‘deafness’ mutants with progressively
more damaged actin binding sites, the structure changes from a well-ordered
crystalline array of filaments to a nematic, liquid crystal-like state,”
said Wong, who also is a researcher at the Frederick
Seitz Materials Research Laboratory on campus and at the university’s Beckman Institute for Advanced
Science and Technology.
In the liquid crystalline state, the bundles maintain their orientation
order – that is, they point roughly along the same direction –
but lose their positional order. These nematic liquid crystals are commonly
used in watch displays and laptop displays.
Wong and his colleagues also found that a mixture of mutant espin and
normal espin would prevent the structural transition from occurring.
If gene expression could turn on the production of just a fraction of
normal espin linkers, a kind of rescue attempt at restoring hearing
could, in principle, be made.
“We have identified the underlying molecular cause for one form
of deafness, and we have identified a mechanism to potentially ‘rescue’
this particular kind of pathology,” Wong said. “Even so,
this is really the first step. This work has relevance to not just human
hearing, but also to artificial sensors.”
The U.S. Department of Energy, National Institutes of Health and National
Science Foundation funded the work.
Editor’s note: To reach Gerard Wong, call 217-265-5254; e-mail: gclwong@illinois.edu.
