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Paper Chase

Heterodimeric capping protein is required for stereocilia length and width regulation.

J. Cell Biol.. Sep 12, 2017.
Avenarius MR, Krey JF, Dumont RA, Morgan CP, Benson CB, Vijayakumar S, Cunningham CL, Scheffer DI, Corey DP, Müller U, Jones SM, Barr-Gillespie PG.

Oregon Hearing Research Center and Vollum Institute, Oregon Health and Science University, Portland, OR gillespp@ohsu.edu.

Abstract:

Control of the dimensions of actin-rich processes like filopodia, lamellipodia, microvilli, and stereocilia requires the coordinated activity of many proteins. Each of these actin structures relies on heterodimeric capping protein (CAPZ), which blocks actin polymerization at barbed ends. Because dimension control of the inner ear's stereocilia is particularly precise, we studied the CAPZB subunit in hair cells. CAPZB, present at ∼100 copies per stereocilium, concentrated at stereocilia tips as hair cell development progressed, similar to the CAPZB-interacting protein TWF2. We deleted Capzb specifically in hair cells using Atoh1-Cre, which eliminated auditory and vestibular function. Capzb-null stereocilia initially developed normally but later shortened and disappeared; surprisingly, stereocilia width decreased concomitantly with length. CAPZB2 expressed by in utero electroporation prevented normal elongation of vestibular stereocilia and irregularly widened them. Together, these results suggest that capping protein participates in stereocilia widening by preventing newly elongating actin filaments from depolymerizing.