XIRP2, an actin-binding protein essential for inner ear hair-cell stereocilia

Cell Rep. 2015 Mar 24;10(11):1811-8. doi: 10.1016/j.celrep.2015.02.042. Epub 2015 Mar 12.

Abstract

Hair cells of the inner ear are mechanoreceptors for hearing and balance, and proteins highly enriched in hair cells may have specific roles in the development and maintenance of the mechanotransduction apparatus. We identified XIRP2/mXinβ as an enriched protein likely to be essential for hair cells. We found that different isoforms of this protein are expressed and differentially located: short splice forms (also called XEPLIN) are targeted more to stereocilia, whereas two long isoforms containing a XIN-repeat domain are in both stereocilia and cuticular plates. Mice lacking the Xirp2 gene developed normal stereocilia bundles, but these degenerated with time: stereocilia were lost and long membranous protrusions emanated from the nearby apical surfaces. At an ultrastructural level, the paracrystalline actin filaments became disorganized. XIRP2 is apparently involved in the maintenance of actin structures in stereocilia and cuticular plates of hair cells, and perhaps in other organs where it is expressed.

Publication types

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

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actin Cytoskeleton / ultrastructure
  • Animals
  • Cytoskeletal Proteins
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Hair Cells, Auditory / metabolism*
  • Hair Cells, Auditory / ultrastructure
  • LIM Domain Proteins / genetics
  • LIM Domain Proteins / metabolism*
  • Mice
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Transport
  • Stereocilia / metabolism*

Substances

  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • LIM Domain Proteins
  • Nuclear Proteins
  • Protein Isoforms
  • XIRP2 protein, mouse