Authors contributed equally to this work.
Differential expression of otoferlin in brain, vestibular system, immature and mature cochlea of the rat
Article first published online: 6 DEC 2006
European Journal of Neuroscience
Volume 24, Issue 12, pages 3372–3380, December 2006
How to Cite
Schug, N., Braig, C., Zimmermann, U., Engel, J., Winter, H., Ruth, P., Blin, N., Pfister, M., Kalbacher, H. and Knipper, M. (2006), Differential expression of otoferlin in brain, vestibular system, immature and mature cochlea of the rat. European Journal of Neuroscience, 24: 3372–3380. doi: 10.1111/j.1460-9568.2006.05225.x
- Issue published online: 12 DEC 2006
- Article first published online: 6 DEC 2006
- Received 9 June 2006, revised 27 September 2006, accepted 9 October 2006
- auditory system;
- Wistar rat
Mutations of the human otoferlin gene lead to an autosomal recessive nonsyndromic form of prelingual, sensorineural deafness (deafness autosomal recessive 9, DFNB9). Several studies have demonstrated expression of otoferlin in the inner ear and brain, and suggested a role of otoferlin in Ca2+-triggered exocytosis. So far, otoferlin expression profiles were solely based on the detection of mRNA. Here, we analysed the expression of otoferlin protein and mRNA using immunohistochemistry, in situ hybridization and RT-PCR in neonatal and mature Wistar rat tissue. In agreement with previous studies, otoferlin expression was found in the brain and in inner and vestibular hair cells. Otoferlin mRNA and protein was, however, also detected in mature outer hair cells of low-frequency processing cochlear turns and in auditory nerve fibres. In outer, inner and vestibular hair cells, otoferlin was subcellularly localized at a considerable distance from the presumed active release sites. Double-staining with the synaptic ribbon marker, C-terminal binding protein 2 (CtBP2), or the presynaptic Ca2+-channel, Cav1.3, both assumed to mark the sites of vesicle fusion and transmitter release, did not colocalize with otoferlin expression and thus do not necessarily support a selected role of otoferlin in Ca2+-triggered exocytosis. The widespread distribution of otoferlin in neurons, nerve fibres and hair cells, and its subcellular distribution extending beyond the regions of synaptic vesicle fusion, i.e. coenrichment with the cytosolic Golgi matrix protein 130 (GM130) in inner hair cells or the early endosomal autoantigen 1 (EEA1) in outer hair cells support instead the idea of a more ubiquitous role of otoferlin in early/recycling endosome trans-Golgi network dynamics.