AP2 Regulates Thickveins Trafficking to Attenuate NMJ Growth Signaling in Drosophila

eNeuro. 2022 Oct 12;9(5):ENEURO.0044-22.2022. doi: 10.1523/ENEURO.0044-22.2022. Print 2022 Sep-Oct.


Compromised endocytosis in neurons leads to synapse overgrowth and altered organization of synaptic proteins. However, the molecular players and the signaling pathways which regulate the process remain poorly understood. Here, we show that σ2-adaptin, one of the subunits of the AP2-complex, genetically interacts with Mad, Medea and Dad (components of BMP signaling) to control neuromuscular junction (NMJ) growth in Drosophila Ultrastructural analysis of σ2-adaptin mutants show an accumulation of large vesicles and membranous structures akin to endosomes at the synapse. We found that mutations in σ2-adaptin lead to an accumulation of Tkv receptors at the presynaptic membrane. Interestingly, the level of small GTPase Rab11 was significantly reduced in the σ2-adaptin mutant synapses. However, expression of Rab11 does not restore the synaptic defects of σ2-adaptin mutations. We propose a model in which AP2 regulates Tkv internalization and endosomal recycling to control synaptic growth.

Keywords: BMP receptors; Rab11; Thickveins; synaptic growth; σ2-adaptin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism
  • Drosophila
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster / metabolism
  • Monomeric GTP-Binding Proteins* / metabolism
  • Neuromuscular Junction / metabolism
  • Protein Serine-Threonine Kinases
  • Receptors, Cell Surface / metabolism
  • Synapses / metabolism


  • Bone Morphogenetic Proteins
  • Drosophila Proteins
  • Receptors, Cell Surface
  • tkv protein, Drosophila
  • Protein Serine-Threonine Kinases
  • Monomeric GTP-Binding Proteins