RRC ID 66062
Author Lasseigne AM, Echeverry FA, Ijaz S, Michel JC, Martin EA, Marsh AJ, Trujillo E, Marsden KC, Pereda AE, Miller AC.
Title Electrical synaptic transmission requires a postsynaptic scaffolding protein.
Journal Elife
Abstract 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.
Volume 10
Published 2021-4-28
DOI 10.7554/eLife.66898
PII 66898
PMID 33908867
PMC PMC8081524
MeSH 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
IF 7.08
Zebrafish Tol-056