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cAMP controls a trafficking mechanism that maintains the neuron specificity and subcellular placement of electrical synapses


Palumbos SDSierra D , Skelton RRachel , McWhirter RRebecca , Mitchell AAmanda , Swann IIsaiah , Heifner SSydney , Von Stetina SStephen , Miller DMDavid M . Developmental cell. 2021 11 05; 56(23). 3235-3249.e4


Electrical synapses are established between specific neurons and within distinct subcellular compartments, but the mechanisms that direct gap junction assembly in the nervous system are largely unknown. Here, we show that a developmental program tunes cAMP signaling to direct the neuron-specific assembly and placement of electrical synapses in the C. elegans motor circuit. We use live-cell imaging to visualize electrical synapses in vivo and an optogenetic assay to confirm that they are functional. In ventral A class (VA) motor neurons, the UNC-4 transcription factor blocks expression of cAMP antagonists that promote gap junction miswiring. In unc-4 mutants, VA electrical synapses are established with an alternative synaptic partner and are repositioned from the VA axon to soma. cAMP counters these effects by driving gap junction trafficking into the VA axon for electrical synapse assembly. Thus, our experiments establish that cAMP regulates gap junction trafficking for the biogenesis of functional electrical synapses.