Expression and function of Rab3 interacting molecules and clarin-1 in inner hair cells

by Tomoko Oshima-Takago
Doctoral thesis
Date of Examination:2013-03-12
Date of issue:2013-09-04
Advisor:Prof. Dr. Tobias Moser
Referee:Prof. Dr. Tobias Moser
Referee:Prof. Dr. Martin Göpfert
Referee:Prof. Dr. Georg Klump
Referee:Prof. Dr. Erwin Neher
Referee:Dr. Dr. Oliver Schlüter
Referee:Ph.D. Camin Dean
Persistent Address: http://dx.doi.org/10.53846/goediss-4010

 

 

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Abstract

English

Hearing depends on faithful synaptic transmission at the inner hair cell (IHC) ribbon synapse, which is orchestrated by active zone proteins. RIM (Rab3 Interacting Molecules) is one of the active zone proteins and proposed to bind not only with multiple other presynaptic proteins, but also with synaptic vesicles and Ca2+ channels. In this study, the expression pattern and functions of RIMs in the IHCs were examined. Wild type IHCs express RIM2alpha and RIM3gamma at their active zone, whereas RIM1 is the major isoform in the CNS. Further electrophysiological analysis revealed that RIM2alpha regulates Ca2+-triggered exocytosis by controlling presynaptic L-type Ca2+ currents at the IHC ribbon synapse. This study clarifies that RIM2alpha underlies the normal hearing by controlling synaptic transmission at the IHCs ribbon synapse. In this thesis, the function of Clarin-1 protein, which is a causal protein for Usher syndrome type III, was also examined at the IHCs ribbon synapse. Although Clarin-1 was proposed to play a role in mechanoelectrical transduction, but the synaptic function remained unclear. The functional analysis demonstrates that Clarin-1 is not essential for synaptic transmission at the auditory first synapse.
Keywords: Synapse; Inner hair cell; Active zone; Usher syndrome; Synaptic transmission; Calcium channel
 
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