Rab8b GTPase, a protein transport regulator, is an interacting partner of otoferlin, defective in a human autosomal recessive deafness form.

Abstract

Mutations within OTOF encoding otoferlin lead to a recessive disorder called DFNB9. Several studies have indicated otoferlin's association with ribbon synapses of cochlear sensory hair cells, as well as data showing the protein's presence in neurons, nerve fibers and hair cells, suggesting a more ubiquitous function. Otoferlin's co-localization not only with ribbon synaptic proteins, but also with additional endosomal (EEA1) or Golgi proteins (GM130) were motivation for a search for further binding partners of otoferlin by a yeast two-hybrid screen in a rodent cochlear cDNA library (P3-P15). This screen identified Rab8b GTPase as a novel interacting partner, substantiated by transient co-expression and co-localization in HEK 293 cells and co-immunoprecipitation of the complex using tagged proteins in vitro and native proteins from cochlea. This finding implies that otoferlin could be a part of components contributing to trans-Golgi trafficking.

• Authors: Paulina Heidrych, Ulrike Zimmermann, Andreas Bress, Carsten M Pusch, Peter Ruth, Markus Pfister, Marlies Knipper, Nikolaus Blin
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 17 Issue 23 Pg. 3814-21 (Dec 01 2008) ISSN: 1460-2083 [Electronic] England
• PMID: 18772196 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Proteins
• Otof protein, rat
• Rab8 protein, mouse
• otoferlin protein, mouse
• Rab8b protein, rat
• rab GTP-Binding Proteins

Topics

• Animals
• Cell Line
• Deafness (genetics, metabolism)
• Genes, Recessive
• Hair Cells, Auditory (metabolism)
• Humans
• Membrane Proteins (genetics, metabolism)
• Protein Binding
• Protein Transport
• Rats
• Rats, Wistar
• Two-Hybrid System Techniques
• rab GTP-Binding Proteins (genetics, metabolism)