AP2 Regulates Thickveins Trafficking to Attenuate NMJ Growth Signaling inDrosophila

Abstract

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 σ2adaptin 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.

Bone morphogenetic protein signaling: the pathway and its regulation

“…Nwk physically interacts with Tkv, with dynamin, and with dap160, components of the endocytic machinery, suggesting that endocytosis attenuates Tkv-mediated BMP signaling. Consistent with a role for endocytosis as a means to reduce BMP signaling, loss of omega2-adaptin, which normally associates with clathrin to mediate endocytosis, results in an increase in Tkv receptors at the presynaptic membrane and in early endosomes, with a concomitant increase in BMP signaling and synaptic growth ( Choudhury et al . 2022 ).…”