The role of adaptor proteins in endosomal sorting during ultrafast endocytosis

总结 内吞作用是大分子、受体、转运蛋白和 通道通过质膜的内化而再循环。内吞作用. 突触，称为突触囊泡内吞作用，支持囊泡的快速恢复 在神经传递过程中。网格蛋白介导的内吞作用发生在刺激后约30秒， 然而，使用“闪光和冻结”电子显微镜，我们已经证明， 在刺激后30 - 300 ms，在两种小鼠海马神经元中的内吞作用 作为C.神经肌肉接头此外，该过程不依赖于网格蛋白。 超快的内吞作用产生一个大的内体， 突触囊泡或靶向溶酶体中的降解。内体分选 需要网格蛋白，但尚不清楚哪些蛋白质作用于内体以靶向这些蛋白质。 囊泡网格蛋白结合衔接蛋白AP 1、AP 2和AP 3都已被研究。 涉及突触功能和靶向膜结合区室。AP 2是 据认为，AP 1和AP 3的作用是再生突触囊泡，而AP 1和AP 3的作用是靶向囊泡 分别连接到质膜或溶酶体上。该奖学金的目标是 确定这些衔接蛋白在内体分选和再生中的作用， 突触囊泡在超快内吞作用。

Summary Endocytosis is a process by which macromolecules, receptors, transporters, and channels are recycled via internalization of the plasma membrane. Endocytosis at synapses, called synaptic vesicle endocytosis, supports the rapid recovery of vesicles during neurotransmission. Clathrin-mediated endocytosis occurs ~ 30 s after stimulation, however using “flash-and-freeze” electron microscopy we have demonstrated endocytosis at 30 – 300 ms after stimulation in both mouse hippocampal neurons as well as C. elegans neuromuscular junctions. Further, the process is clathrin independent. Ultrafast endocytosis generates a large endosome, which much be sorted into new synaptic vesicles or targeted for degradation in the lysosomes. Sorting of the endosome requires clathrin, but it is not clear which proteins act on the endosome to target these vesicles. The clathrin binding adaptor proteins AP1, AP2, and AP3 have all been implicated in synaptic function and targeting of membrane bound compartments. AP2 is thought to regenerate synaptic vesicles, while AP1 and AP3 are thought to target vesicles to the plasma membrane or the lysosome, respectively. The goal of this fellowship is to determine the role of these adaptor proteins in endosomal sorting and regeneration of synaptic vesicles during ultrafast endocytosis.