title: BMP signaling and microtubule organization regulate synaptic strength.
abstract: The strength of synaptic transmission between a neuron and multiple postsynaptic partners can vary considerably. We have studied synaptic heterogeneity using the glutamatergic Drosophila neuromuscular junction (NMJ), which contains multiple synaptic connections of varying strengths between a motor axon and muscle fiber. In larval NMJs, there is a gradient of synaptic transmission from weak proximal to strong distal boutons. We imaged synaptic transmission with the postsynaptically targeted fluorescent calcium sensor SynapCam, to investigate the molecular pathways that determine synaptic strength and set up this gradient. We discovered that mutations in the Bone Morphogenetic Protein (BMP) signaling pathway disrupt production of strong distal boutons. We find that strong connections contain unbundled microtubules in the boutons, suggesting a role for microtubule organization in transmission strength. The spastin mutation, which disorganizes microtubules, disrupted the transmission gradient, supporting this interpretation. We propose that the BMP pathway, shown previously to function in the homeostatic regulation of synaptic growth, also boosts synaptic transmission in a spatially selective manner that depends on the microtubule system.
authors: Department of Molecular and Cell Biology and the Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, United States.
authors: R W
authors: RW
authors: Ball
authors: Department of Molecular and Cell Biology and the Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, United States.
authors: E S
authors: ES
authors: Peled
authors: Department of Molecular and Cell Biology and the Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, United States.
authors: G
authors: G
authors: Guerrero
authors: Department of Molecular and Cell Biology and the Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, United States; Physical Bioscience Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, United States. Electronic address: ehud@berkeley.edu.
authors: E Y
authors: EY
authors: Isacoff
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005456:Fluorescent Dyes; C112506:MAD protein, Drosophila; D008869:Microtubule-Associated Proteins; D011956:Receptors, Cell Surface; D014157:Transcription Factors; C409635:futsch protein, Drosophila; C449821:wit protein, Drosophila; D000251:Adenosine Triphosphatases; C501874:spas protein, Drosophila; D002118:Calcium
keywords: Bone Morphogenetic Protein signaling pathway; drosophila; fluorescent calcium sensor; microtubule; neuromuscular junction; synaptic transmission