Scientists identify molecular cause for one form of
deafness
Editor: Scientists continue to identify a variety of genetic causes
for deafness, and I admit that I haven't tried to keep track of them
all. This looks to me like a new one with an interesting mechanism!
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February 2007
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.
