Highwire regulates presynaptic BMP signaling essential for synaptic growth.

Full 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.

Author information

Author/s: McCabe, Brian D (BD); Hom, Sabrina (S); Aberle, Hermann (H); Fetter, Richard D (RD); Marques, Guillermo (G); Haerry, Theodore E (TE); Wan, Hong (H); O'Connor, Michael B (MB); Goodman, Corey S (CS); Haghighi, A Pejmun (AP);

Affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. bmccabe(-atsign-)socrates.berkeley.edu

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Neuron (Neuron), published in United States. (Language: eng)

Reference: 2004-Mar; vol 41 (issue 6) : pp 891-905

Dates: Created 2004/03/29; Completed 2004/05/20; Revised 2006/11/15;

PMID: 15046722, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals
Bone Morphogenetic Proteins - genetics; metabolism
Cell Differentiation - genetics
Cell Size - genetics
DNA-Binding Proteins - genetics; metabolism
Drosophila Proteins - genetics; metabolism
Drosophila melanogaster - growth & development; metabolism; ultrastructure
Microscopy, Electron
Motor Neurons - cytology; metabolism
Mutation - genetics

Nerve Tissue Proteins - genetics; metabolism
Neuromuscular Junction - growth & development; metabolism; ultrastructure
Presynaptic Terminals - metabolism; pathology; ultrastructure
Protein Binding - genetics
Receptors, Cell Surface - genetics; metabolism
Receptors, Transforming Growth Factor beta - genetics; metabolism
Signal Transduction - genetics
Smad4 Protein
Synaptic Transmission - genetics
Trans-Activators - genetics; metabolism

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Bone Morphogenetic Proteins (0) ; DNA-Binding Proteins (0) ; Drosophila Proteins (0) ; Medea protein, Drosophila (0) ; Nerve Tissue Proteins (0) ; Receptors, Cell Surface (0) ; Receptors, Transforming Growth Factor beta (0) ; Smad4 Protein (0) ; Trans-Activators (0) ; highwire protein, Drosophila (0) ; sax protein, Drosophila (0) ; wit protein, Drosophila (0)

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