Drosophila VAP-33A Directs Bouton Formation at Neuromuscular Junctions in a Dosage-Dependent Manner

Neuron. 2002 Jul 18;35(2):291-306. doi: 10.1016/s0896-6273(02)00769-9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axonal Transport / genetics
  • Carrier Proteins / genetics
  • Carrier Proteins / isolation & purification*
  • Cell Differentiation / physiology
  • Cytoskeleton / genetics
  • Cytoskeleton / metabolism
  • Cytoskeleton / ultrastructure
  • Drosophila Proteins*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development*
  • Drosophila melanogaster / metabolism
  • Female
  • Gene Dosage*
  • Gene Expression Regulation, Developmental / physiology
  • Genetic Testing
  • Immunohistochemistry
  • Insect Proteins / metabolism
  • Male
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / isolation & purification*
  • Microscopy, Electron
  • Microtubules / metabolism*
  • Microtubules / ultrastructure
  • Molecular Sequence Data
  • Mutation / genetics
  • Nervous System / growth & development*
  • Nervous System / metabolism
  • Nervous System / ultrastructure
  • Neuromuscular Junction / growth & development*
  • Neuromuscular Junction / metabolism
  • Neuromuscular Junction / ultrastructure
  • Presynaptic Terminals / metabolism*
  • Presynaptic Terminals / ultrastructure
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Signal Transduction / physiology
  • Synaptic Membranes / metabolism
  • Synaptic Membranes / ultrastructure
  • Tumor Suppressor Proteins / metabolism
  • Vesicular Transport Proteins*

Substances

  • Carrier Proteins
  • Drosophila Proteins
  • Insect Proteins
  • Membrane Proteins
  • Tumor Suppressor Proteins
  • VAPA protein, human
  • Vap33 protein, Drosophila
  • Vesicular Transport Proteins
  • dlg1 protein, Drosophila