SNARE-dependence of the exocytosis at the inner hair cell ribbon synapse

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The sensory senses provide the organism with information about the external world. For example, processing of acoustic information requires transduction of sound stimuli in the inner ear encoding by hair cells. The synapses of the inner hair cells (IHCs) with the auditory nerve fibers are characterized by an electron dense structure called synaptic ribbon, which is packed with synaptic vesicles and anchored to the presynaptic membrane. Although powerful molecular biological and biophysical techniques have initiated major progress in investigating ribbon synapse, its molecular physiology is still poorly understood. During exocytosis in most synapses, a four-helical coiled coil protein complex is formed, between the three SNARE proteins syntaxin 1, synaptobrevin 2 and SNAP-25, bridging vesicle and plasma membrane. This SNARE complex is essential for priming and fusion of synaptic vesicles and is probably also present in IHCs. However, the function of the SNARE proteins at ribbon synapses remains elusive. In order to gain more insight in the SNARE function at the IHCs synapse, the objective of this grant application is to study the effects of the clostridial neurotoxins, which interfere with SNARE function by protein cleavage, on the IHCs exocytosis.