Drosophila VAP-33A directs bouton formation at neuromuscular junctions in a dosage-dependent manner.
Aplysia VAP-33 (VAMP-associated protein) has been previously proposed to be involved in the control of neurotransmitter release. Here, we show that a Drosophila homolog of VAP-33, DVAP-33A, is localized to neuromuscular junctions. Loss of DVAP-33A causes a severe decrease in the number of boutons and a corresponding increase in bouton size. Conversely, presynaptic overexpression of DVAP-33A induces an increase in the number of boutons and a decrease in their size. Gain-of-function experiments show that the presynaptic dose of DVAP-33A tightly modulates the number of synaptic boutons. Our data also indicate that the presynaptic microtubule architecture is severely compromised in DVAP-33A mutants. We propose that a DVAP-33A-mediated interaction between microtubules and presynaptic membrane plays a pivotal role during bouton budding.
Pennetta
Giuseppa
G
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
Hiesinger
Peter Robin
PR
Fabian-Fine
Ruth
R
Meinertzhagen
Ian A
IA
Bellen
Hugo J
HJ
D000818:Animals; D001370:Axonal Transport / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification*; D002454:Cell Differentiation / Q000502:physiology; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D005260:Female; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005820:Genetic Testing; D007150:Immunohistochemistry; D019476:Insect Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000302:isolation & purification*; D008854:Microscopy, Electron; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009420:Nervous System / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction / Q000502:physiology; D013570:Synaptic Membranes / Q000378:metabolism / Q000648:ultrastructure; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins; C114051:VAPA protein, human; C491921:Vap33 protein, Drosophila; D033921:Vesicular Transport Proteins; C070350:dlg1 protein, Drosophila
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