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J Biol Chem. 2015 Jul 17;290(29):17656-67. doi: 10.1074/jbc.M115.644583. Epub 2015 May 7.

The Neurexin/N-Ethylmaleimide-sensitive Factor (NSF) Interaction Regulates Short Term Synaptic Depression.

Author information

1
From the Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096 and.
2
From the Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096 and the Co-innovation Center of Neuroregeneration, Nantong University, Nantong, JS 226001, China.
3
From the Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096 and the Co-innovation Center of Neuroregeneration, Nantong University, Nantong, JS 226001, China junhaihan@seu.edu.cn.

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.

KEYWORDS:

Drosophila; SNARE proteins; neurotransmitter release; synapse; synaptic plasticity; yeast two-hybrid

PMID:
25953899
PMCID:
PMC4505015
DOI:
10.1074/jbc.M115.644583
[Indexed for MEDLINE]
Free PMC Article

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