TY - JOUR
T1 - Heterodimeric capping protein is required for stereocilia length and width regulation
AU - Avenarius, Matthew R.
AU - Krey, Jocelyn F.
AU - Dumont, Rachel A.
AU - Morgan, Clive P.
AU - Benson, Connor B.
AU - Vijayakumar, Sarath
AU - Cunningham, Christopher L.
AU - Scheffer, Deborah I.
AU - Corey, David P.
AU - Müller, Ulrich
AU - Jones, Sherri M.
AU - Barr-Gillespie, Peter G.
N1 - Publisher Copyright:
© 2017 Avenarius et al.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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 CAP ZB subunit in hair cells. CAP ZB, present at ~100 copies per stereocilium, concentrated at stereocilia tips as hair cell development progressed, similar to the CAP ZB-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. CAP ZB2 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.
AB - 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 CAP ZB subunit in hair cells. CAP ZB, present at ~100 copies per stereocilium, concentrated at stereocilia tips as hair cell development progressed, similar to the CAP ZB-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. CAP ZB2 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.
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U2 - 10.1083/jcb.201704171
DO - 10.1083/jcb.201704171
M3 - Article
C2 - 28899994
AN - SCOPUS:85032979675
SN - 0021-9525
VL - 216
SP - 3861
EP - 3881
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 11
ER -