TitleAP2 regulates Thickveins trafficking to attenuate NMJ growth signaling in .
Publication TypeJournal Article
Year of Publication2022
AuthorsChoudhury SDey, Dwivedi MKumar, Pippadpally S, Patnaik A, Mishra S, Padinjat R, Kumar V
JournaleNeuro
Date Published2022 Sep 30
ISSN2373-2822
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 Ultrastructural analysis of mutants show an accumulation of large vesicles and membranous structures akin to endosomes at the synapse. We found that mutations in lead to an accumulation of Tkv receptors at the presynaptic membrane. Interestingly, the level of small GTPase Rab11 was significantly reduced in the mutant synapses. However, expression of Rab11 does not restore the synaptic defects of mutations. We propose a model in which AP2 regulates Tkv internalization and endosomal recycling to control synaptic growth.Understanding the regulation of synaptic development and refinement could provide mechanistic insights into the neural basis of fundamental processes such as learning, memory and adaptation. In this study, we describe the role of σ-adaptin in attenuating NMJ growth signaling and show its involvement in the trafficking of Thickveins receptor at the NMJ. σ-adaptin interacts genetically with the BMP pathway components and NMJ synapses lacking σ-adaptin show reduced levels of the endosomal recycling marker, Rab11. Our study contributes to a broader understanding of AP2 complex-dependent regulation of synaptic growth signaling, which might have implications in neurodevelopment under conditions where endocytosis and trafficking of the BMP receptors are perturbed.

DOI10.1523/ENEURO.0044-22.2022
Alternate JournaleNeuro
PubMed ID36180220