title: Crimpy enables discrimination of presynaptic and postsynaptic pools of a BMP at the Drosophila neuromuscular junction.
abstract: Distinct pools of the bone morphogenetic protein (BMP) Glass bottom boat (Gbb) control structure and function of the Drosophila neuromuscular junction. Specifically, motoneuron-derived Gbb regulates baseline neurotransmitter release, whereas muscle-derived Gbb regulates neuromuscular junction growth. Yet how cells differentiate between these ligand pools is not known. Here we present evidence that the neuronal Gbb-binding protein Crimpy (Cmpy) permits discrimination of pre- and postsynaptic ligand by serving sequential functions in Gbb signaling. Cmpy first delivers Gbb to dense core vesicles (DCVs) for activity-dependent release from presynaptic terminals. In the absence of Cmpy, Gbb is no longer associated with DCVs and is not released by activity. Electrophysiological analyses demonstrate that Cmpy promotes Gbb's proneurotransmission function. Surprisingly, the Cmpy ectodomain is itself released upon DCV exocytosis, arguing that Cmpy serves a second function in BMP signaling. In addition to trafficking Gbb to DCVs, we propose that Gbb/Cmpy corelease from presynaptic terminals defines a neuronal protransmission signal.
authors.affiliation: Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: James
authors.affiliation: Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Kendall M
authors.initials: KM
authors.lastname: Hoover
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Dinara
authors.initials: D
authors.lastname: Bulgari
authors.affiliation: Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Colleen N
authors.initials: CN
authors.lastname: McLaughlin
authors.affiliation: Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wilson
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, USA.
authors.forename: Kristi A
authors.initials: KA
authors.lastname: Wharton
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Edwin S
authors.initials: ES
authors.lastname: Levitan
authors.affiliation: Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Electronic address: heather.broihier@case.edu.
authors.forename: Heather T
authors.initials: HT
authors.lastname: Broihier
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D016212:Transforming Growth Factor beta; C000595489:cmpy protein, Drosophila; C089440:gbb protein, Drosophila