Identification of a novel Cochlin isoform in the perilymph: insights to Cochlin function and the pathogenesis of DFNA9

Biochem Biophys Res Commun. 2004 Feb 6;314(2):440-6. doi: 10.1016/j.bbrc.2003.12.106.

Abstract

The COCH gene mutated in DFNA9, an autosomal dominant hereditary sensorineural hearing loss and vestibular disorder, encodes Cochlin. Previously, we reported three bovine Cochlin isoforms, p63s, p44s, and p40s, which exhibit significant molecular heterogeneity in vivo. Here we have characterized Cochlin isoforms by generating four isoform-specific anti-Cochlin antibodies. The same three Cochlin isoforms, p63s, p44s, and p40s, were detected in human and cow inner ear tissue; however, p44s and p40s were not detected in perilymph. We identified a novel short 16kDa isoform in human perilymph and a 18-23kDa isoform in cow perilymph, named Cochlin-tomoprotein (CTP), corresponding to the N-terminus of full-length Cochlin (p63s) and the LCCL domain. Notably, CTP contains all of the known mutation sites associated with DFNA9. The pathogenesis of DFNA9 is not fully clarified as yet, and this novel perilymph-associated CTP isoform might provide mechanistic clues to how mutations in the COCH gene damage the inner ear function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • Cattle
  • Deafness
  • Ear, Inner / metabolism
  • Electrophoresis, Gel, Two-Dimensional
  • Electrophoresis, Polyacrylamide Gel
  • Extracellular Matrix Proteins
  • Humans
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Peptides / chemistry
  • Perilymph / metabolism*
  • Protein Isoforms
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Sequence Homology, Amino Acid
  • Time Factors

Substances

  • COCH protein, human
  • Extracellular Matrix Proteins
  • Peptides
  • Protein Isoforms
  • Proteins