Multilayer control of KaiR1D-autoreceptor function by the auxiliary protein Neto
Wen-Chieh Hsieh1, Tae Hee Han1, Rosario Vicidomini1
1Section on Cellular Communication, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, 20892, USA.
Biorxiv : the Preprint Server for Biology
|November 24, 2025
Summary
Neto-α auxiliary protein regulates kainate-type glutamate receptors (KaiR1D) in Drosophila. Neto-α controls receptor function and distribution, enhancing neurotransmitter release and synaptic stability.
Area of Science:
- Neuroscience
- Molecular Biology
- Synaptic Plasticity
Background:
- Kainate-type glutamate receptors and Neto auxiliary proteins are crucial for synaptic network regulation.
- Specific roles of Neto and kainate receptors in synaptic function remain challenging to delineate.
Purpose of the Study:
- To investigate the role of Neto in regulating kainate-type glutamate receptors (KaiR1D) at the Drosophila neuromuscular junction.
- To elucidate how Neto modulates autoreceptor activity and neurotransmitter release.
Main Methods:
- In vivo studies of Neto-α's effect on KaiR1D presynaptic accumulation and function.
- Outside-out patch recordings to analyze KaiR1D gating properties modulated by Neto-α.
- Assessment of Neto-α's impact on KaiR1D axonal distribution and synaptic transmission.
Main Results:
- Neto-α limits presynaptic KaiR1D autoreceptor accumulation and function in vivo.
- Neto-α modulates KaiR1D gating, slowing desensitization and reducing sensitivity to blockers.
- Neto-α enhances presynaptic charge transfer and Ca2+ influx, increasing neurotransmitter release.
Conclusions:
- Neto-α provides multi-layered regulation of KaiR1D autoreceptors, ensuring proper neurotransmitter release.
- Coordinated regulation of receptor function and localization by auxiliary subunits is an ancestral strategy for synaptic stability.
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