PUBLICATION

Complexes of Usher proteins preassemble at the endoplasmic reticulum and are required for trafficking and ER homeostasis

Authors
Blanco-Sánchez, B., Clément, A., Fierro, J., Washbourne, P., Westerfield, M.
ID
ZDB-PUB-140513-359
Date
2014
Source
Disease models & mechanisms   7: 547-59 (Journal)
Registered Authors
Blanco, Bernardo, Clément, Aurélie, Washbourne, Philip, Westerfield, Monte
Keywords
Cadherin23, ER stress, Hair cell, Harmonin, Ift88, Myo7aa, Trafficking, Usher syndrome, Zebrafish
MeSH Terms
  • Adaptor Proteins, Signal Transducing/genetics
  • Adaptor Proteins, Signal Transducing/metabolism*
  • Animals
  • Endoplasmic Reticulum/metabolism*
  • Endoplasmic Reticulum Stress
  • Hair Cells, Auditory, Inner
  • Homeostasis*
  • Mechanoreceptors/metabolism
  • Multiprotein Complexes/metabolism*
  • Mutation/genetics
  • Protein Binding
  • Protein Transport
  • Subcellular Fractions/metabolism
  • Transport Vesicles/metabolism
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
24626987 Full text @ Dis. Model. Mech.
Abstract
Usher syndrome (USH), the leading cause of hereditary combined hearing and vision loss, is characterized by sensorineural deafness and progressive retinal degeneration. Mutations in several different genes produce USH, but the proximal cause of sensory cell death remains mysterious. We adapted a proximity ligation assay to analyze associations among three of the USH proteins, Cdh23, Harmonin and Myo7aa, and the microtubule-based transporter Ift88 in zebrafish inner ear mechanosensory hair cells. We found that the proteins are in close enough proximity to form complexes and that these complexes preassemble at the endoplasmic reticulum (ER). Defects in any one of the three USH proteins disrupt formation and trafficking of the complex and result in diminished levels of the other proteins, generalized trafficking defects and ER stress that triggers apoptosis. ER stress, thus, contributes to sensory hair cell loss and provides a new target to explore for protective therapies for USH.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes