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

感官为生物体提供有关外部世界的信息。例如，声音信息的处理需要内耳中由毛细胞编码的声音刺激转导。内毛细胞（IHCs）与听神经纤维的突触具有一种称为突触带的电子密集结构的特征，该结构充满突触囊泡并固定在突触前膜上。尽管强大的分子生物学和生物物理学技术在研究带状突触方面取得了重大进展，但其分子生理学仍然知之甚少。在大多数突触胞吐过程中，在三个SNARE蛋白syntaxin 1、synaptobrevin 2和SNAP-25之间形成一个四螺旋螺旋状的coil蛋白复合物，架起囊泡和质膜的桥梁。SNARE复合体对于突触囊泡的启动和融合至关重要，可能也存在于ihc中。然而，SNARE蛋白在带状突触中的功能仍然难以捉摸。为了更深入地了解ihc突触的SNARE功能，本申请的目的是研究梭状菌神经毒素对ihc胞外分泌的影响，梭状菌神经毒素通过蛋白质裂解干扰SNARE功能。

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.