The Amino Acid Transporter JhI-21 Coevolves with Glutamate Receptors, Impacts NMJ Physiology, and Influences Locomotor Activity in Drosophila Larvae.

Anna B Ziegler,Martine Berthelot-Grosjean,Yael Grosjean,David E Featherstone,Joern R Steinert,Gérard Manière,Flore Geillon,Hrvoje Augustin,Nathan L Clark,Mégane M Simonnet

doi:10.1038/srep19692

Abstract

Changes in synaptic physiology underlie neuronal network plasticity and behavioral phenomena, which are adjusted during development. The Drosophila larval glutamatergic neuromuscular junction (NMJ) represents a powerful synaptic model to investigate factors impacting these processes. Amino acids such as glutamate have been shown to regulate Drosophila NMJ physiology by modulating the clustering of postsynaptic glutamate receptors and thereby regulating the strength of signal transmission from the motor neuron to the muscle cell. To identify amino acid transporters impacting glutmatergic signal transmission, we used Evolutionary Rate Covariation (ERC), a recently developed bioinformatic tool. Our screen identified ten proteins co-evolving with NMJ glutamate receptors. We selected one candidate transporter, the SLC7 (Solute Carrier) transporter family member JhI-21 (Juvenile hormone Inducible-21), which is expressed in Drosophila larval motor neurons. We show that JhI-21 suppresses postsynaptic muscle glutamate receptor abundance, and that JhI-21 expression in motor neurons regulates larval crawling behavior in a developmental stage-specific manner.

Highlights

Changes in synaptic physiology underlie neuronal network plasticity and behavioral phenomena, which are adjusted during development
JhI-21 is identified as a component of the glutamatergic signaling pathway by Evolutionary Rate Covariation (ERC)
Even though metabotropic and ionotropic glutamate receptors are not co-localized within the same cell at the neuromuscular junction (NMJ) of 3rd-instar larvae, they do act in the same intercellular signaling pathway and the ERC values between the two different types of receptors are very high

Summary

Introduction

Changes in synaptic physiology underlie neuronal network plasticity and behavioral phenomena, which are adjusted during development. The Drosophila larval glutamatergic neuromuscular junction (NMJ) represents a powerful synaptic model to investigate factors impacting these processes Amino acids such as glutamate have been shown to regulate Drosophila NMJ physiology by modulating the clustering of postsynaptic glutamate receptors and thereby regulating the strength of signal transmission from the motor neuron to the muscle cell. For example, we identified a glial amino acid exchanger, Genderblind (GB), which is capable of tuning synaptic strength by regulating the amount of extracellular glutamate. This glutamate constitutively desensitizes ionotropic glutamate receptors (iGluRs), inhibits their clustering, and thereby suppresses synaptic transmission[4,5].

Methods

Results

Conclusion