Neto-α Controls Synapse Organization and Homeostasis at the Drosophila Neuromuscular Junction.

• 发表时间: 07 2020 7
• 来源期刊: Cell Rep
• DOI: 10.1016/j.celrep.2020.107866
• PMID: 32640231
• 文章类型: Journal Article
• 作者列表: Han TH,Vicidomini R,Ramos CI,Wang Q,Nguyen P,Jarnik M,Lee CH,Stawarski M,Hernandez RX,Macleod GT,Serpe M

关键词: Drosophila neuromuscular junction; Neto; auxiliary proteins; ionotropic glutamate receptors; synapse development; synapse homeostasis

Mesh: Animals; Calcium / metabolism; Drosophila Proteins / chemistry metabolism; Drosophila melanogaster / metabolism ultrastructure; Homeostasis; Membrane Proteins / chemistry metabolism; Neuromuscular Junction / metabolism ultrastructure; Post-Synaptic Density / ultrastructure; Protein Domains; Receptors, Glutamate / metabolism; Synapses / metabolism

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 postsynaptic 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-α functions on both sides of the NMJ. In muscle, Neto-α limits the size of the postsynaptic receptor field. In motor neurons (MNs), Neto-α controls neurotransmitter release in a KAR-dependent manner. In addition, Neto-α is both required and sufficient for the presynaptic increase in neurotransmitter release in response to reduced postsynaptic sensitivity. This KAR-independent function of Neto-α is involved in activity-induced cytomatrix remodeling. We propose that Drosophila ensures NMJ functionality by acquiring two Neto isoforms with differential expression patterns and activities.