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

Abstract:

: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 (15)N-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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Drummond MC,Barzik M,Bird JE,Zhang DS,Lechene CP,Corey DP,Cunningham LL,Friedman TB

doi

10.1038/ncomms7873

subject

Has Abstract

pub_date

2015-04-21 00:00:00

pages

6873

issn

2041-1723

pii

ncomms7873

journal_volume

6

pub_type

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