Molecular physiology of synaptic vesicle recycling at the hair cell ribbon synapse (A08*)

为了维持高速率的突触传递，内毛细胞（IHC）需要有效地回收突触囊泡。然而，很少有人知道SV回收的机制在IHC带状突触。在这里，我们计划测试以下假设：在IHC中：1）AP-2有助于胞吐-胞吞偶联和/或网格蛋白涂层在质膜和内体样空泡处的组装; 2）在内吞膜回收期间和内体顺式转运的囊泡重组期间，发动蛋白在裂变中起作用;以及3）内亲蛋白以及synaptojanin介导网格蛋白涂层囊泡的脱涂层。为了实现这一目标，我们将对相关小鼠突变体的免疫组化突触进行形态和功能研究

In order to sustain high rates of synaptic transmission, inner hair cells (IHCs) need to efficiently recycle synaptic vesicles. Yet, little is known about the mechanisms of SV recycling at IHC ribbon synapses. Here we plan to test the hypotheses that in IHCs: 1) AP-2 contributes to exocytosis-endocytosis coupling and/or clathrin coat assembly at the plasma membrane and endosomal-like vacuoles; 2) dynamins operate in fission during endocytic membrane retrieval and during vesicle reformation from endosomal cisterns; and 3) endophilins as well as synaptojanin mediate uncoating of clathrin-coated vesicles. To achieve this we will carry out morphological and functional studies of IHC synapses in relevant mouse mutants