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

为了维持高的突触传递率，内毛细胞（IHCs）需要有效地回收突触囊泡。然而，对IHC带状突触的SV再循环机制知之甚少。在此，我们计划验证以下假设：1)AP-2有助于胞外-内吞偶联和/或质膜和内核体样液泡处的网格蛋白外壳组装；2)动力蛋白在内吞膜回收和内体囊泡重构过程中参与裂变；3)亲内啡肽和突触蛋白介导网格蛋白包被囊泡的脱包。为了实现这一目标，我们将在相关小鼠突变体中开展IHC突触的形态学和功能研究

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