AMPK adapts metabolism to developmental energy requirement during dendrite pruning in Drosophila.

Marco Marzano,Neeraja Sanal,Svende Herzmann,Leonardo Elsbroek,Erez Raz,Katsiaryna Tarbashevich,Sebastian Rumpf,Michael P Krahn

doi:10.1016/j.celrep.2021.110024

Marco Marzano, Neeraja Sanal + Show 6 more

Open Access

https://doi.org/10.1016/j.celrep.2021.110024

Copy DOI

Abstract

To reshape neuronal connectivity in adult stages, Drosophila sensory neurons prune their dendrites during metamorphosis using a genetic degeneration program that is induced by the steroid hormone ecdysone. Metamorphosis is a nonfeeding stage that imposes metabolic constraints on development. We find that AMP-activated protein kinase (AMPK), a regulator of energy homeostasis, is cell-autonomously required for dendrite pruning. AMPK is activated by ecdysone and promotes oxidative phosphorylation and pyruvate usage, likely to enable neurons to use noncarbohydrate metabolites such as amino acids for energy production. Loss of AMPK or mitochondrial deficiency causes specific defects in pruning factor translation and the ubiquitin-proteasome system. Our findings distinguish pruning from pathological neurite degeneration, which is often induced by defects in energy production, and highlight how metabolism is adapted to fit energy-costly developmental transitions.

Highlights

Neurite pruning, the degeneration of neurites without loss of the parent neuron, is a conserved mechanism that serves to specify neuronal connections or to remove developmental intermediates (Riccomagno and Kolodkin, 2015)
Dendrite pruning is regulated in a cell-intrinsic manner by the steroid hormone ecdysone through a transcriptional cascade that leads to the expression of specific pruning factors such as the transcription factor Sox14 and the actin-severing enzyme Mical (Kirilly et al, 2009; Kuo et al, 2005; Williams and Truman, 2005)
AMPK is required for c4 da neuron dendrite pruning We identified AMPK in a screen for phosphoregulators of c4 da neuron dendrite pruning

Summary

Introduction

The degeneration of neurites without loss of the parent neuron, is a conserved mechanism that serves to specify neuronal connections or to remove developmental intermediates (Riccomagno and Kolodkin, 2015). Dendrite pruning is regulated in a cell-intrinsic manner by the steroid hormone ecdysone through a transcriptional cascade that leads to the expression of specific pruning factors such as the transcription factor Sox and the actin-severing enzyme Mical (Kirilly et al, 2009; Kuo et al, 2005; Williams and Truman, 2005). Many important pruning mechanisms consume ATP, such as transcription (Kirilly et al, 2009), translation (Rode et al, 2018), and proteasomal proteolysis (Kuo et al, 2005; Rumpf et al, 2011; Wong et al, 2013)

Methods

Discussion

Conclusion