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Citation
Rui, M., Qian, J., Liu, L., Cai, Y., Lv, H., Han, J., Jia, Z., Xie, W. (2017). The neuronal protein Neurexin directly interacts with the Scribble-Pix complex to stimulate F-actin assembly for synaptic vesicle clustering.  J. Biol. Chem. 292(35): 14334--14348.
FlyBase ID
FBrf0236511
Publication Type
Research paper
Abstract

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.

PubMed ID
PubMed Central ID
PMC5582829 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Biol. Chem.
    Title
    Journal of Biological Chemistry
    Publication Year
    1905-
    ISBN/ISSN
    0021-9258
    Data From Reference
    Aberrations (2)
    Alleles (17)
    Genes (8)
    Human Disease Models (1)
    Physical Interactions (3)
    Natural transposons (1)
    Insertions (1)
    Experimental Tools (4)
    Transgenic Constructs (11)