title: The Neurexin/N-Ethylmaleimide-sensitive Factor (NSF) Interaction Regulates Short Term Synaptic Depression.
abstract: Although Neurexins, which are cell adhesion molecules localized predominantly to the presynaptic terminals, are known to regulate synapse formation and synaptic transmission, their roles in the regulation of synaptic vesicle release during repetitive nerve stimulation are unknown. Here, we show that nrx mutant synapses exhibit rapid short term synaptic depression upon tetanic nerve stimulation. Moreover, we demonstrate that the intracellular region of NRX is essential for synaptic vesicle release upon tetanic nerve stimulation. Using a yeast two-hybrid screen, we find that the intracellular region of NRX interacts with N-ethylmaleimide-sensitive factor (NSF), an enzyme that mediates soluble NSF attachment protein receptor (SNARE) complex disassembly and plays an important role in synaptic vesicle release. We further map the binding sites of each molecule and demonstrate that the NRX/NSF interaction is critical for both the distribution of NSF at the presynaptic terminals and SNARE complex disassembly. Our results reveal a previously unknown role of NRX in the regulation of short term synaptic depression upon tetanic nerve stimulation and provide new mechanistic insights into the role of NRX in synaptic vesicle release.
authors.affiliation: Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096.
authors.forename: Yao
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096.
authors.forename: Huiying
authors.initials: H
authors.lastname: Chen
authors.affiliation: Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096.
authors.forename: Huihui
authors.initials: H
authors.lastname: Lv
authors.affiliation: Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, JS 226001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, JS 226001, China. Electronic address: junhaihan@seu.edu.cn.
authors.forename: Junhai
authors.initials: J
authors.lastname: Han
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D036881:Long-Term Synaptic Depression; D008969:Molecular Sequence Data; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000032:analysis / Q000378:metabolism*; D009473:Neuronal Plasticity; D060066:Protein Interaction Maps; D017434:Protein Structure, Tertiary; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D013572:Synaptic Vesicles / Q000235:genetics / Q000502:physiology
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; C491321:Nrx protein, Drosophila; D052066:N-Ethylmaleimide-Sensitive Proteins
keywords: Drosophila; SNARE proteins; neurotransmitter release; synapse; synaptic plasticity; yeast two-hybrid