Neto-α controls synapse organization and homeostasis at the Drosophila neuromuscular junction

Abstract

Glutamate receptor auxiliary proteins control receptor distribution and function, ultimately controlling synapse assembly, maturation and plasticity. At the Drosophila neuromuscular junction (NMJ), a synapse with both pre- and post-synaptic kainate-type glutamate receptors (KARs), we show that the auxiliary protein Neto evolved functionally distinct isoforms to modulate synapse development and homeostasis. Using genetics, cell biology and electrophysiology we demonstrate that Neto- functions on both sides of the NMJ. In muscle, Neto- limits the size of the postsynaptic receptors field. In motor neurons, Neto- controls neurotransmitter release in a KAR-dependent manner. Furthermore, Neto- is both required and sufficient for the presynaptic increase in neurotransmitter release in response to reduced postsynaptic sensitivity. This KAR-independent function of Neto- is involved in activity-induced cytomatrix remodeling. We propose that Drosophila ensured NMJ functionality by acquiring two Neto isoforms with differential expression patterns and activities.