β-actin and fascin-2 cooperate to maintain stereocilia length

Benjamin J. Perrin, Dana M. Strandjord, Praveena Narayanan, Davin M. Henderson, Kenneth R. Johnson, James M. Ervasti

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Stereocilia are actin-based protrusions on auditory sensory hair cells that are deflected by sound waves to initiate the conversion of mechanical energy to neuronal signals. Stereocilia maintenance is essential because auditory hair cells are not renewed in mammals. This process requires both β-actin and γ-actin as knock-out mice lacking either isoform develop distinct stereocilia pathology during aging. In addition, stereocilia integrity may hinge on immobilizing actin, which outside of a small region at stereocilia tips turns over with a very slow, months-long half-life. Here, we establish that β-actin and the actin crosslinking protein fascin-2 cooperate to maintain stereocilia length and auditory function. We observed that mice expressing mutant fascin-2 (p.R109H) or mice lacking β-actin share a common phenotype including progressive, high-frequency hearing loss together with shortening of a defined subset of stereocilia in the hair cell bundle. Fascin-2 binds β-actin and γ-actin filaments with similar affinity in vitro and fascin-2 does not depend on β-actin for localization in vivo. Nevertheless, double-mutant mice lacking β-actin and expressing fascin-2 p.R109H have a more severe phenotype suggesting that each protein has a different function in a common stereocilia maintenance pathway. Because the fascin-2 p.R109H mutant binds but fails to efficiently crosslink actin filaments, we propose that fascin-2 crosslinks function to slow actin depolymerization at stereocilia tips to maintain stereocilia length.

Original languageEnglish (US)
Pages (from-to)8114-8121
Number of pages8
JournalJournal of Neuroscience
Volume33
Issue number19
DOIs
StatePublished - May 13 2013

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Stereocilia
Actins
Auditory Hair Cells
Actin Cytoskeleton
fascin
High-Frequency Hearing Loss
Maintenance
Phenotype
Knockout Mice
Half-Life
Mammals
Protein Isoforms
Proteins

Cite this

Perrin, B. J., Strandjord, D. M., Narayanan, P., Henderson, D. M., Johnson, K. R., & Ervasti, J. M. (2013). β-actin and fascin-2 cooperate to maintain stereocilia length. Journal of Neuroscience, 33(19), 8114-8121. https://doi.org/10.1523/JNEUROSCI.0238-13.2013

β-actin and fascin-2 cooperate to maintain stereocilia length. / Perrin, Benjamin J.; Strandjord, Dana M.; Narayanan, Praveena; Henderson, Davin M.; Johnson, Kenneth R.; Ervasti, James M.

In: Journal of Neuroscience, Vol. 33, No. 19, 13.05.2013, p. 8114-8121.

Research output: Contribution to journalArticle

Perrin, BJ, Strandjord, DM, Narayanan, P, Henderson, DM, Johnson, KR & Ervasti, JM 2013, 'β-actin and fascin-2 cooperate to maintain stereocilia length', Journal of Neuroscience, vol. 33, no. 19, pp. 8114-8121. https://doi.org/10.1523/JNEUROSCI.0238-13.2013
Perrin BJ, Strandjord DM, Narayanan P, Henderson DM, Johnson KR, Ervasti JM. β-actin and fascin-2 cooperate to maintain stereocilia length. Journal of Neuroscience. 2013 May 13;33(19):8114-8121. https://doi.org/10.1523/JNEUROSCI.0238-13.2013
Perrin, Benjamin J. ; Strandjord, Dana M. ; Narayanan, Praveena ; Henderson, Davin M. ; Johnson, Kenneth R. ; Ervasti, James M. / β-actin and fascin-2 cooperate to maintain stereocilia length. In: Journal of Neuroscience. 2013 ; Vol. 33, No. 19. pp. 8114-8121.
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