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Live-cell imaging of actin dynamics reveals mechanisms of stereocilia length regulation in the inner ear

Drummond, Meghan C. ; Barzik, Melanie ; Bird, Jonathan E. ; Zhang, Duan-Sun ; Lechene, Claude P. ; Corey, David P. ; Cunningham, Lisa L. ; Friedman, Thomas B.

Drummond, Meghan C., Melanie Barzik, Jonathan E. Bird, Duan-Sun Zhang, Claude P. Lechene, David P. Corey, Lisa L. Cunningham, and Thomas B. Friedman. 2015. “Live-cell imaging of actin dynamics reveals mechanisms of stereocilia length regulation in the inner ear.” Nature Communications 6 (1): 6873. doi:10.1038/ncomms7873. http://dx.doi.org/10.1038/ncomms7873. [Peer Reviewed Journal]

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  • Title:
    Live-cell imaging of actin dynamics reveals mechanisms of stereocilia length regulation in the inner ear
  • Author: Drummond, Meghan C. ; Barzik, Melanie ; Bird, Jonathan E. ; Zhang, Duan-Sun ; Lechene, Claude P. ; Corey, David P. ; Cunningham, Lisa L. ; Friedman, Thomas B.
  • Subjects: Actins -- Physiology ; Ear, Inner -- Cytology ; Stereocilia -- Physiology
  • Is Part Of: Drummond, Meghan C., Melanie Barzik, Jonathan E. Bird, Duan-Sun Zhang, Claude P. Lechene, David P. Corey, Lisa L. Cunningham, and Thomas B. Friedman. 2015. “Live-cell imaging of actin dynamics reveals mechanisms of stereocilia length regulation in the inner ear.” Nature Communications 6 (1): 6873. doi:10.1038/ncomms7873. http://dx.doi.org/10.1038/ncomms7873.
  • Description: The maintenance of sensory hair cell stereocilia is critical for lifelong hearing; however, mechanisms of structural homeostasis remain poorly understood. Conflicting models propose that stereocilia F-actin cores are either continually renewed every 24–48 h via a treadmill or are stable, exceptionally long-lived structures. Here to distinguish between these models, we perform an unbiased survey of stereocilia actin dynamics in more than 500 utricle hair cells. Live-imaging EGFP-β-actin or dendra2-β-actin reveal stable F-actin cores with turnover and elongation restricted to stereocilia tips. Fixed-cell microscopy of wild-type and mutant β-actin demonstrates that incorporation of actin monomers into filaments is required for localization to stereocilia tips. Multi-isotope imaging mass spectrometry and live imaging of single differentiating hair cells capture stereociliogenesis and explain uniform incorporation of 15N-labelled protein and EGFP-β-actin into nascent stereocilia. Collectively, our analyses support a model in which stereocilia actin cores are stable structures that incorporate new F-actin only at the distal tips.
  • Language: English
  • Identifier: ISSN: 2041-1723 ; DOI: 10.1038/ncomms7873

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