Neurotransmitters are released from synapses by the fusion of synaptic vesicles with the plasma membrane. Synaptic vesicles must first dock to the plasma membrane, become primed for fusion, respond to calcium and fuse. Synaptic vesicle exocytosis is mediated in part by the SNARE proteins (syntaxin, synaptobrevin and SNAP-25), UNC-18 and the novel protein RIC-7. We will answer the following questions: What is the role of UNC-18 in exocytosis? 1. Is UNC-18 a direct regulator of docking? 2. Is UNC-18 required for the disassembly of the SNARE complex so that these proteins can function in subsequent rounds of exocytosis? 3. Does UNC-18 inhibit the formation of the SNARE complex by binding syntaxin? What is the role of SNARE proteins in exocytosis? 4. Is syntaxin required for docking? Is syntaxin required for fusion? 5. Is synaptobrevin required for docking? Is it required redundantly with synaptotagmin for docking? Is synaptobrevin required for fusion? Is it required redundantly with synaptotagmin to present synaptic vesicles to syntaxin? What is the role of RIC-7 in exocytosis? 6. RIC-7 is a novel protein required at the synapse. Is RIC-7 required for docking? Is RIC-7 required for priming, calcium sensing, or fusion? These studies will explore the molecular mechanisms of nervous system function. A molecular understanding of the synapse will provide us with the knowledge base that will be required to treat neurodegenerative disorders such as Alzheimer's Disease, to treat autoimmune diseases like Rasmussen's encephalitis, and genetic disorders of the nervous system.
| Watanabe, Shigeki; Mamer, Lauren Elizabeth; Raychaudhuri, Sumana et al. (2018) Synaptojanin and Endophilin Mediate Neck Formation during Ultrafast Endocytosis. Neuron 98:1184-1197.e6 |
| Kurshan, Peri T; Merrill, Sean A; Dong, Yongming et al. (2018) ?-Neurexin and Frizzled Mediate Parallel Synapse Assembly Pathways Antagonized by Receptor Endocytosis. Neuron 100:150-166.e4 |
| Alqadah, Amel; Hsieh, Yi-Wen; Schumacher, Jennifer A et al. (2016) SLO BK Potassium Channels Couple Gap Junctions to Inhibition of Calcium Signaling in Olfactory Neuron Diversification. PLoS Genet 12:e1005654 |
| Hollopeter, Gunther; Lange, Jeffrey J; Zhang, Ying et al. (2014) The membrane-associated proteins FCHo and SGIP are allosteric activators of the AP2 clathrin adaptor complex. Elife 3: |
| Watanabe, Shigeki; Trimbuch, Thorsten; Camacho-Pérez, Marcial et al. (2014) Clathrin regenerates synaptic vesicles from endosomes. Nature 515:228-33 |
| Ailion, Michael; Hannemann, Mandy; Dalton, Susan et al. (2014) Two Rab2 interactors regulate dense-core vesicle maturation. Neuron 82:167-80 |
| Kavalali, Ege T; Jorgensen, Erik M (2014) Visualizing presynaptic function. Nat Neurosci 17:10-6 |
| Rawson, Randi L; Yam, Lung; Weimer, Robby M et al. (2014) Axons degenerate in the absence of mitochondria in C. elegans. Curr Biol 24:760-5 |
| Watanabe, Shigeki; Liu, Qiang; Davis, M Wayne et al. (2013) Ultrafast endocytosis at Caenorhabditis elegans neuromuscular junctions. Elife 2:e00723 |
| Peden, Aude S; Mac, Patrick; Fei, You-Jun et al. (2013) Betaine acts on a ligand-gated ion channel in the nervous system of the nematode C. elegans. Nat Neurosci 16:1794-801 |
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