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- Title
UNC-43/CaMKII-triggered anterograde signals recruit GABA<sub>A</sub>Rs to mediate inhibitory synaptic transmission and plasticity at C. elegans NMJs.
- Authors
Hao, Yue; Liu, Haowen; Zeng, Xian-Ting; Wang, Ya; Zeng, Wan-Xin; Qian, Kang-Ying; Li, Lei; Chi, Ming-Xuan; Gao, Shangbang; Hu, Zhitao; Tong, Xia-Jing
- Abstract
Disturbed inhibitory synaptic transmission has functional impacts on neurodevelopmental and psychiatric disorders. An essential mechanism for modulating inhibitory synaptic transmission is alteration of the postsynaptic abundance of GABAARs, which are stabilized by postsynaptic scaffold proteins and recruited by presynaptic signals. However, how GABAergic neurons trigger signals to transsynaptically recruit GABAARs remains elusive. Here, we show that UNC-43/CaMKII functions at GABAergic neurons to recruit GABAARs and modulate inhibitory synaptic transmission at C. elegans neuromuscular junctions. We demonstrate that UNC-43 promotes presynaptic MADD-4B/Punctin secretion and NRX-1α/Neurexin surface delivery. Together, MADD-4B and NRX-1α recruit postsynaptic NLG-1/Neuroligin and stabilize GABAARs. Further, the excitation of GABAergic neurons potentiates the recruitment of NLG-1-stabilized-GABAARs, which depends on UNC-43, MADD-4B, and NRX-1. These data all support that UNC-43 triggers MADD-4B and NRX-1α, which act as anterograde signals to recruit postsynaptic GABAARs. Thus, our findings elucidate a mechanism for pre- and postsynaptic communication and inhibitory synaptic transmission and plasticity. The pre-and postsynaptic communication is critical for faithful synaptic transmission and induction of synaptic plasticity. Here, the authors found that CaMKII functions at GABAergic neurons to recruit GABAARs by triggering anterograde signals.
- Subjects
NEUROPLASTICITY; CAENORHABDITIS elegans; NEURAL transmission; GABAERGIC neurons; SCAFFOLD proteins; MYONEURAL junction
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-37137-0