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The neuronal protein Neurexin directly interacts with the Scribble–Pix complex to stimulate F-actin assembly for synaptic vesicle clustering
Synaptic vesicles (SVs) form distinct pools at synaptic terminals, and this well-regulated separation is necessary for normal neurotransmission. However, how the SV cluster, in particular synaptic compartments, maintains normal neurotransmitter release remains a mystery. The presynaptic protein Neur...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582829/ https://www.ncbi.nlm.nih.gov/pubmed/28710284 http://dx.doi.org/10.1074/jbc.M117.794040 |
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author | Rui, Menglong Qian, Jinjun Liu, Lijuan Cai, Yihan Lv, Huihui Han, Junhai Jia, Zhengping Xie, Wei |
author_facet | Rui, Menglong Qian, Jinjun Liu, Lijuan Cai, Yihan Lv, Huihui Han, Junhai Jia, Zhengping Xie, Wei |
author_sort | Rui, Menglong |
collection | PubMed |
description | Synaptic vesicles (SVs) form distinct pools at synaptic terminals, and this well-regulated separation is necessary for normal neurotransmission. However, how the SV cluster, in particular synaptic compartments, maintains normal neurotransmitter release remains a mystery. The presynaptic protein Neurexin (NRX) plays a significant role in synaptic architecture and function, and some evidence suggests that NRX is associated with neurological disorders, including autism spectrum disorders. However, the role of NRX in SV clustering is unclear. Here, using the neuromuscular junction at the 2–3 instar stages of Drosophila larvae as a model and biochemical imaging and electrophysiology techniques, we demonstrate that Drosophila NRX (DNRX) plays critical roles in regulating synaptic terminal clustering and release of SVs. We found that DNRX controls the terminal clustering and release of SVs by stimulating presynaptic F-actin. Furthermore, our results indicate that DNRX functions through the scaffold protein Scribble and the GEF protein DPix to activate the small GTPase Ras-related C3 Botulinum toxin substrate 1 (Rac1). We observed a direct interaction between the C-terminal PDZ-binding motif of DNRX and the PDZ domains of Scribble and that Scribble bridges DNRX to DPix, forming a DNRX–Scribble–DPix complex that activates Rac1 and subsequently stimulates presynaptic F-actin assembly and SV clustering. Taken together, our work provides important insights into the function of DNRX in regulating SV clustering, which could help inform further research into pathological neurexin-mediated mechanisms in neurological disorders such as autism. |
format | Online Article Text |
id | pubmed-5582829 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-55828292017-09-05 The neuronal protein Neurexin directly interacts with the Scribble–Pix complex to stimulate F-actin assembly for synaptic vesicle clustering Rui, Menglong Qian, Jinjun Liu, Lijuan Cai, Yihan Lv, Huihui Han, Junhai Jia, Zhengping Xie, Wei J Biol Chem Neurobiology Synaptic vesicles (SVs) form distinct pools at synaptic terminals, and this well-regulated separation is necessary for normal neurotransmission. However, how the SV cluster, in particular synaptic compartments, maintains normal neurotransmitter release remains a mystery. The presynaptic protein Neurexin (NRX) plays a significant role in synaptic architecture and function, and some evidence suggests that NRX is associated with neurological disorders, including autism spectrum disorders. However, the role of NRX in SV clustering is unclear. Here, using the neuromuscular junction at the 2–3 instar stages of Drosophila larvae as a model and biochemical imaging and electrophysiology techniques, we demonstrate that Drosophila NRX (DNRX) plays critical roles in regulating synaptic terminal clustering and release of SVs. We found that DNRX controls the terminal clustering and release of SVs by stimulating presynaptic F-actin. Furthermore, our results indicate that DNRX functions through the scaffold protein Scribble and the GEF protein DPix to activate the small GTPase Ras-related C3 Botulinum toxin substrate 1 (Rac1). We observed a direct interaction between the C-terminal PDZ-binding motif of DNRX and the PDZ domains of Scribble and that Scribble bridges DNRX to DPix, forming a DNRX–Scribble–DPix complex that activates Rac1 and subsequently stimulates presynaptic F-actin assembly and SV clustering. Taken together, our work provides important insights into the function of DNRX in regulating SV clustering, which could help inform further research into pathological neurexin-mediated mechanisms in neurological disorders such as autism. American Society for Biochemistry and Molecular Biology 2017-09-01 2017-07-14 /pmc/articles/PMC5582829/ /pubmed/28710284 http://dx.doi.org/10.1074/jbc.M117.794040 Text en © 2017 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version free via Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0) . |
spellingShingle | Neurobiology Rui, Menglong Qian, Jinjun Liu, Lijuan Cai, Yihan Lv, Huihui Han, Junhai Jia, Zhengping Xie, Wei The neuronal protein Neurexin directly interacts with the Scribble–Pix complex to stimulate F-actin assembly for synaptic vesicle clustering |
title | The neuronal protein Neurexin directly interacts with the Scribble–Pix complex to stimulate F-actin assembly for synaptic vesicle clustering |
title_full | The neuronal protein Neurexin directly interacts with the Scribble–Pix complex to stimulate F-actin assembly for synaptic vesicle clustering |
title_fullStr | The neuronal protein Neurexin directly interacts with the Scribble–Pix complex to stimulate F-actin assembly for synaptic vesicle clustering |
title_full_unstemmed | The neuronal protein Neurexin directly interacts with the Scribble–Pix complex to stimulate F-actin assembly for synaptic vesicle clustering |
title_short | The neuronal protein Neurexin directly interacts with the Scribble–Pix complex to stimulate F-actin assembly for synaptic vesicle clustering |
title_sort | neuronal protein neurexin directly interacts with the scribble–pix complex to stimulate f-actin assembly for synaptic vesicle clustering |
topic | Neurobiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582829/ https://www.ncbi.nlm.nih.gov/pubmed/28710284 http://dx.doi.org/10.1074/jbc.M117.794040 |
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