Heterodimeric capping protein is required for stereocilia length and width regulation

J Cell Biol. 2017 Nov 6;216(11):3861-3881. doi: 10.1083/jcb.201704171. Epub 2017 Sep 12.

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.

Publication types

  • Video-Audio Media
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Auditory Threshold
  • Behavior, Animal
  • Brain Stem / metabolism
  • Brain Stem / physiopathology
  • CapZ Actin Capping Protein / deficiency
  • CapZ Actin Capping Protein / genetics
  • CapZ Actin Capping Protein / metabolism*
  • Chick Embryo
  • Cilia / metabolism
  • Cilia / ultrastructure
  • Evoked Potentials, Auditory, Brain Stem
  • Gene Expression Regulation, Developmental
  • Genotype
  • Hair Cells, Auditory / metabolism*
  • Hair Cells, Auditory / ultrastructure
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mass Spectrometry
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Otoacoustic Emissions, Spontaneous
  • Phenotype
  • Vestibular Evoked Myogenic Potentials
  • Vestibule, Labyrinth / metabolism
  • Vestibule, Labyrinth / physiopathology

Substances

  • CAPZB protein, mouse
  • CapZ Actin Capping Protein
  • Intracellular Signaling Peptides and Proteins
  • Microfilament Proteins
  • PLEKHO1 protein, mouse
  • Ptk9 protein, mouse

Associated data

  • GENBANK/S11150
  • RefSeq/NM_009798