CAPZB action in hair cells. (A) Model for capping protein interaction with actin. The β-tentacle of CAPZB (dark green) wraps around the first actin subunit (of three shown; magenta). CAPZA also binds to actin with its tentacle. Panel A was modified from Kim et al. (2010) with permission. (B) Model for action of capping protein in widening; the four stereocilia cartoons indicate sequential steps in the process. New actin filaments polymerize from the stereocilia base to the tip, alongside the preexisting original actin paracrystal. Capping protein transiently binds to elongating filaments, preventing their depolymerization when actin monomers are not available. (C) Development of hair cells with or without CAPZB. The middle trajectory indicates how stereocilia lengthening and widening proceed in a wild-type hair cell, with capping protein indicated using the same color scheme as in A and B. CAPZB enters stereocilia after the initial lengthening step and is present during widening. CAPZB accumulates at stereocilia tips, at least in shorter stereocilia. The lower trajectory diagrams the narrowing and shortening of stereocilia that occurs after CAPZB is lost. CAPZB derived from hair-cell progenitors is present in Capzb^CKO even after levels drop in the soma, presumably slowing the shortening and narrowing process. The top trajectory shows the cessation of stereocilia elongation that occurs when MYC-CAPZB2 is expressed in hair cells, as well as the abnormal stereocilia widening. MYC-CAPZB2 is represented with blue subunits, both as monomers and as heterodimers with CAPZA subunits. The placement of the MYC-CAPZB2 and CAPZA molecules in the MYC-CAPZB2 scenario is based on their presumed localization. (D) Diagram of interactions between capping protein (CP), TWF2, and PLEKHO1. The N terminus of CAPZB, which is not directly involved in binding actin filaments, binds to either TWF2 (shown with bound actin monomers) or PLEKHO1.