Synaptic vesicle recycling by clathrin-mediated endocytosis

Synapses are the places where neurons communicate with their targets. At chemical synapses, neurotransmitters are contained in synaptic vesicles and are released into the synaptic cleft upon fusion with the plasma membrane. This event happens at high frequency at synapses and thus synaptic vesicles need to be regenerated locally to prevent vesicle depletion. The popular model for synaptic vesicle endocytosis is to re-sort vesicle proteins left in the plasma membrane into an invaginated vesicle by clathrin-mediated endocytosis. However, some pieces of evidence suggest that clathrin-independent endocytosis might also contribute to synaptic vesicle recycling. In this dissertation, we present the studies on endocytic accessory proteins from clathrin-mediated endocytosis and focus primarily on their potential roles in neurotransmission by using the genetic model organism Caenorhabditis elegans. The proteins investigated include the major adaptor complex AP2, the synaptotagmin adaptor UNC-41 and the membrane bending protein, Epsin. We demonstrate that, one; AP2 is responsible for 70% synaptic vesicle recycling in C. elegans. Second, synaptic recycling of synaptotagmin requires UNC-41. Third, Epsin is not required for curvature acquisition in clathrin-mediated endocytosis at synapses. Thus these studies push forward our understanding towards synaptic vesicle recycling at synapses and demonstrate clathrinmediated endocytosis is likely the major mechanism for synaptic vesicle endocytosis in C. elegans.