Developmental elimination of electrical synapses by UNC-51/UNC-76-mediated vesicular transport
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Updated: Nov 7, 2026

An Optical Assay for Synaptic Vesicle Recycling in Cultured Neurons Overexpressing Presynaptic Proteins
Published on: June 26, 2018
Hao Huang1, Yuzhi Yang1, Yuanhao Xu1
1Department of Neurology of Second Affiliated Hospital, Centre for Cellular Biology and Signaling and Cluster for Organogenesis & Homeostasis, International Joint Center for Biomedical Sciences, Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Abstract:
Neural circuit maturation requires precise elimination of transient synaptic connections, but how electrical synapses are eliminated remains unknown. Using Caenorhabditis elegans PLM mechanosensory neurons, we found that gap junctions form transiently during early development and are subsequently eliminated as the circuit matures. These transient electrical synapses drive high-frequency calcium oscillations; optogenetic ablation of early gap junctions abolishes calcium dynamics and disrupts chemical synapse formation, while restoring calcium activity independently of gap junction coupling substantially rescues this defect, directly linking electrical synapse-driven calcium dynamics to chemical synapse formation. Through forward genetic screening, we identified the conserved kinase UNC-51/ULK as essential for elimination. UNC-51 phosphorylates the kinesin adaptor UNC-76/FEZ to promote RAB-10-dependent net retrograde removal of innexins, progressively depleting innexin proteins from the synaptic site. Disrupting this pathway prevents elimination, causing persistent electrical synapses and neuronal hyperactivity. These findings establish a conserved framework for developmental elimination of functionally essential transient electrical connectivity.
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