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Neuron
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Neuron
Article . 2004
License: Elsevier Non-Commercial
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Neuron
Article . 2004 . Peer-reviewed
License: Elsevier Non-Commercial
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Neuron
Article . 2004
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Highwire Regulates Presynaptic BMP Signaling Essential for Synaptic Growth

Authors: Brian D. McCabe; Sabrina Hom; Hong Wan; Theodore E Haerry; Hermann Aberle; Michael B. O'Connor; Corey S. Goodman; +3 Authors

Highwire Regulates Presynaptic BMP Signaling Essential for Synaptic Growth

Abstract

Highwire (Hiw), a putative RING finger E3 ubiquitin ligase, negatively regulates synaptic growth at the neuromuscular junction (NMJ) in Drosophila. hiw mutants have dramatically larger synaptic size and increased numbers of synaptic boutons. Here we show that Hiw binds to the Smad protein Medea (Med). Med is part of a presynaptic bone morphogenetic protein (BMP) signaling cascade consisting of three receptor subunits, Wit, Tkv, and Sax, in addition to the Smad transcription factor Mad. When compared to wild-type, mutants of BMP signaling components have smaller NMJ size, reduced neurotransmitter release, and aberrant synaptic ultrastructure. BMP signaling mutants suppress the excessive synaptic growth in hiw mutants. Activation of BMP signaling, which in wild-type does not cause additional growth, in hiw mutants does lead to further synaptic expansion. These results reveal a balance between positive BMP signaling and negative regulation by Highwire, governing the growth of neuromuscular synapses.

Keywords

Motor Neurons, Neuroscience(all), Neuromuscular Junction, Presynaptic Terminals, Cell Differentiation, Nerve Tissue Proteins, Receptors, Cell Surface, Synaptic Transmission, DNA-Binding Proteins, Microscopy, Electron, Drosophila melanogaster, Bone Morphogenetic Proteins, Mutation, Trans-Activators, Animals, Drosophila Proteins, Receptors, Transforming Growth Factor beta, Cell Size, Protein Binding, Signal Transduction, Smad4 Protein

  • BIP!
    Impact byBIP!
    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    208
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
208
Top 10%
Top 10%
Top 1%
hybrid