Deafness, Liquid Crystals, and Flaccid Stereocilia

Yeah, I know what you must be thinking: What a weird and ridiculous title. However, trust me, it actually does make sense. In yesterday's basic concepts post on Hearing, I explained that sound is transduced in the inner ear by hair cells in the cochlea. Specifically, that the deflection of hair cells' "hairs" (the stereocillia) cause ions to enter the cell and subsequently stimulate nerves which project to auditory processing centers. All this depends on the stereocillia being properly formed and rigid----but what happens if the stereocillia are too floppy?

A recent discovery by a team at the Univeristy of Illinois at Urbana-Champaign has pinpointed a specific protein---espin---which is extremely important for the proper structure of these stereocillia. In fact, mutations in this protein cause deafness.

(Contined below the fold.....)

Espin's role in a cell is that of architect and glue. It organizes filimentous actin (f-actin) into bundles and links them, providing the necessary structural framework for stereocillia to function. Mice (and humans) which have genetic defects in espin binding sites are deaf, because normal espin is replaced with an espin mutant which changes the rigidity of the stereocillia.

"The interior structure of the bundles changes from a rigid, hexagonal array of uniformly twisted filaments, to a liquid crystalline arrangement of filaments," [Dr. Gerard] 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."

For comparison (and to get a better idea of why espin is important), take a look at the below figures from Rzadzinska et al. (2005). They examined what would happen if the espin protein was over-expressed or reduced. Their hypothesis was that since espin promotes f-actin linking in stereocilia, more espin would lengthen the stereocilia and less espin would shorten them. In fact, this is exactly what was found.

The stereocilia bundles in green have been over-expressing espin, resulting in abnormally long stereocilia. Normal stereocilia are red.

Rows of outer hair cells' stereocilia. Compared to the normal espin expression levels (A), decreased espin expression in mouse mutants also reduces stereocilia length, making them abnormally short.

Rzadzinska et al. 2005. Balanced Levels of Espin are Critical for Stereociliary Growth and Length Maintenance. Cell Motility and the Cytoskeleton 62:157-165.

Purdy et al. 2007. Structural Polymorphism of the Actin-Espin System: A Prototypical System of Filaments and Linkers in Stereocilia. Physical Review Letters. 98. (HT: Bob Abu)