Journal
ELIFE
Volume 10, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.66898
Keywords
-
Categories
Funding
- Eunice Kennedy Shriver National Institute of Child Health and Human Development [T32HD007348, F32HD102182]
- National Institute on Deafness and Other Communication Disorders [R01DC011099]
- National Institute of Neurological Disorders and Stroke [R21NS085772, R21NS117967, R01NS105758]
- National Institute of Mental Health [RF1MH120016]
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
Ask authors/readers for more resources
This study investigated the functional relationship between neuronal Connexins and ZO1, revealing that ZO1 is crucial for the localization of synaptic Connexins, while Connexins are not necessary for ZO1 localization. Disruption of this hierarchical ZO1/Connexin relationship abolishes electrical transmission and disrupts Mauthner cell-initiated escape responses.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available