ZFIN ID: ZDB-PUB-210429-4
Electrical synaptic transmission requires a postsynaptic scaffolding protein
Lasseigne, A.M., Echeverry, F.A., Ijaz, S., Michel, J.C., Martin, E.A., Marsh, A.J., Trujillo, E., Marsden, K.C., Pereda, A.E., Miller, A.C.
Date: 2021
Source: eLIFE   10: (Journal)
Registered Authors: Marsden, Kurt, Marsh, Audrey, Miller, Adam
Keywords: connexins, developmental biology, electrical coupling, electrical synapse, gap junctions, neuroscience, synapse formation, zebrafish, zo1 zo-1
MeSH Terms:
  • Animals
  • Connexins/metabolism*
  • Electrical Synapses/physiology*
  • Synaptic Transmission/genetics*
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • Zonula Occludens-1 Protein/genetics*
  • Zonula Occludens-1 Protein/metabolism
PubMed: 33908867 Full text @ Elife
Electrical synaptic transmission relies on neuronal gap junctions containing channels constructed by Connexins. While at chemical synapses neurotransmitter-gated ion channels are critically supported by scaffolding proteins, it is unknown if channels at electrical synapses require similar scaffold support. Here, we investigated the functional relationship between neuronal Connexins and Zonula Occludens 1 (ZO1), an intracellular scaffolding protein localized to electrical synapses. Using model electrical synapses in zebrafish Mauthner cells, we demonstrated that ZO1 is required for robust synaptic Connexin localization, but Connexins are dispensable for ZO1 localization. Disrupting this hierarchical ZO1/Connexin relationship abolishes electrical transmission and disrupts Mauthner cell-initiated escape responses. We found that ZO1 is asymmetrically localized exclusively postsynaptically at neuronal contacts where it functions to assemble intercellular channels. Thus, forming functional neuronal gap junctions requires a postsynaptic scaffolding protein. The critical function of a scaffolding molecule reveals an unanticipated complexity of molecular and functional organization at electrical synapses.