Neurobeachin controls the asymmetric subcellular distribution of electrical synapse proteins

E Anne Martin; Jennifer Carlisle Michel; Jane S. Kissinger; Fabio A. Echeverry; Ya-Ping Lin; John O'Brien; Alberto E. Pereda; Adam C. Miller

doi:10.1016/j.cub.2023.04.049

Back

Neurobeachin controls the asymmetric subcellular distribution of electrical synapse proteins

Journal article

Open access

Peer reviewed

Neurobeachin controls the asymmetric subcellular distribution of electrical synapse proteins

E Anne Martin, Jennifer Carlisle Michel, Jane S. Kissinger, Fabio A. Echeverry, Ya-Ping Lin, John O'Brien, Alberto E. Pereda and Adam C. Miller

Current biology, Vol.33(10), pp.2063-2074.e4

05/22/2023

DOI: 10.1016/j.cub.2023.04.049

PMCID: PMC10266475

PMID: 37172585

Files and links (1)

url

https://doi.org/10.1016/j.cub.2023.04.049View

Published (Version of record) Open Access

Abstract

The subcellular positioning of synapses and their specialized molecular compositions form the fundamental basis of neural circuits. Like chemical synapses, electrical synapses are constructed from an assortment of adhesion, scaffolding, and regulatory molecules, yet little is known about how these molecules localize to specific neuronal compartments. Here, we investigate the relationship between the autism-and epilepsy -associated gene Neurobeachin, the neuronal gap junction channel-forming Connexins, and the electrical synapse scaffold ZO1. Using the zebrafish Mauthner circuit, we find Neurobeachin localizes to the electrical synapse independently of ZO1 and Connexins. By contrast, we show Neurobeachin is required postsynap-tically for the robust localization of ZO1 and Connexins. We demonstrate that Neurobeachin binds ZO1 but not Connexins. Finally, we find Neurobeachin is required to restrict electrical postsynaptic proteins to den-drites, but not electrical presynaptic proteins to axons. Together, the results reveal an expanded understand-ing of electrical synapse molecular complexity and the hierarchical interactions required to build neuronal gap junctions. Further, these findings provide novel insight into the mechanisms by which neurons compart-mentalize the localization of electrical synapse proteins and provide a cell biological mechanism for the sub -cellular specificity of electrical synapse formation and function.

Cell Biology

Biochemistry & Molecular Biology

Biology

Life Sciences & Biomedicine

Life Sciences & Biomedicine - Other Topics

Science & Technology

Details

Title: Subtitle: Neurobeachin controls the asymmetric subcellular distribution of electrical synapse proteins
Creators: E Anne Martin - University of Oregon
Jennifer Carlisle Michel - University of Oregon
Jane S. Kissinger - University of Oregon
Fabio A. Echeverry - Albert Einstein College of Medicine
Ya-Ping Lin - Univ Texas Hlth Sci Ctr Houston, Dept Ophthalmol & Visual Sci, Houston, TX 77030 USA
John O'Brien - Univ Texas Hlth Sci Ctr Houston, Dept Ophthalmol & Visual Sci, Houston, TX 77030 USA
Alberto E. Pereda - Albert Einstein College of Medicine
Adam C. Miller - University of Oregon
Resource Type: Journal article
Publication Details: Current biology, Vol.33(10), pp.2063-2074.e4
DOI: 10.1016/j.cub.2023.04.049
PMID: 37172585
PMCID: PMC10266475
NLM abbreviation: Curr Biol
ISSN: 0960-9822
eISSN: 1879-0445
Publisher: Elsevier
Number of pages: 17
Grant note: RF1MH120016; R21NS085772; R01DC011099; R01EY012857; R21NS117967; R01NS105758 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA F32HD102182 / Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Language: English
Date published: 05/22/2023
Academic Unit: Iowa Neuroscience Institute; Biology
Record Identifier: 9984937941802771

Metrics

9 Record Views