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.

Insulin is present all across the animal kingdom. Its proper release after feeding is of extraordinary importance for nutrient uptake, regulation of metabolism, and growth. We used Drosophila melanogaster to shed light on the processes linking dietary leucine intake to insulin secretion. The Drosophila genome encodes 8 insulin-like peptides ("Dilps"). Of these, Dilp2 is secreted after the ingestion of a leucine-containing diet. We previously demonstrated that Minidiscs, related to mammalian system-L transporters, acts as a leucine sensor within the Dilp2-secreting insulin-producing cells ("IPCs") of the brain. Here, we show that a second leucine transporter, JhI-21, of the same family is additionally necessary for proper leucine sensing in the IPCs. Using calcium imaging and ex-vivo cultured brains we show that knockdown of JhI-21 in IPCs causes malfunction of these cells: they are no longer able to sense dietary leucine or to release Dilp2 in a leucine dependent manner. JhI-21 knockdown in IPCs further causes systemic metabolic defects including defective sugar uptake and altered growth. Finally, we showed that JhI-21 and Minidiscs have no cumulative effect on Dilp2 release. Since system-L transporters are expressed by mammalian β-cells our results could help to better understand the role of these proteins in insulin signaling.