Uncovering the electrical synapse proteome in retinal neurons via in vivo proximity labeling.
Overview
- College of Optometry, University of Houston Houston United States
- Moran Eye Center/Ophthalmology, University of Utah Salt Lake City United States
- Animal Navigation/ Neurosensorics, Institute for Biology and Environmental Sciences, University of Oldenburg Oldenburg Germany
- Research Center Neurosensory Science, University of Oldenburg Oldenburg Germany
- Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine Bronx United States
- Institute-Associated Research Group: Cell Adhesion and Cell Polarity, Institute of Medical Biochemistry, ZMBE, University of Münster Münster Germany
- Cell Signal Unit, Okinawa Institute of Science and Technology Onna-son Japan
Abstract
Electrical synapses containing Connexin 36 (Cx36) represent the main means for direct electrical communication among neurons in the mammalian nervous system. However, little is known about the protein complexes that constitute these synapses. In the present study, we applied different BioID strategies to screen the interactomes of Connexin 36 and its zebrafish orthologue Cx35.1 in retinal neurons. For in vivo proximity labeling in mice, we took advantage of the Cx36-EGFP strain and expressed a GFP-nanobody-TurboID fusion construct selectively in AII amacrine cells. For in vivo BioID in zebrafish, we generated a transgenic line expressing a Cx35.1-TurboID fusion under control of the Cx35.1 promoter. Both strategies allowed us to capture a plethora of molecules that were associated with electrical synapses and showed a high degree of evolutionary conservation in the proteomes of both species. Besides known interactors of Cx36 such as ZO-1 and ZO-2, we have identified more than 50 new proteins, such as scaffold proteins, adhesion molecules, and regulators of the cytoskeleton. Moreover, we determined the subcellular localization of these proteins in mouse retina and tested potential binding interactions with Cx36. Among these new interactors, we identified signal-induced proliferation associated 1 like 3 (Sipa1l3), a protein that has been implicated in cell junction formation and cell polarity, as a new scaffold of electrical synapses. Interestingly, Sipa1l3 was able to interact with ZO-1, ZO-2, and Cx36, suggesting a pivotal role in electrical synapse function. In summary, our study provides the first detailed view of the electrical synapse proteome in retinal neurons, which is likely to apply to electrical synapses elsewhere.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
The paper links to its data, not to its authors' code: see the Data section.
Tracing map
A tracing map links a paper to the code its authors published: this paper has none, so it has no map.
Data
Datasets cited
- biostudies:S-BIAD3071, at BioStudies; found in “Data availability”
Data availability
The mass spectrometry data that were collected in this study are available as supplementary files. Confocal and gel images are stored in a data repository and can be found at https://
The following dataset was generated:
TetenborgS 2026Uncovering the electrical synapse proteome in retinal neurons via in vivo proximity labelingBioimage ArchiveS-BIAD307110.7554
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 28 September 2026: the first record
Recorded: type, language, journal, volume, pages, dates, 14 authors, 8 keywords, 10 MeSH terms, 4 funders, 73 references, 48 RRIDs.
Cite
This paper
Tetenborg, S., Shihabeddin, E., Kumar, E. O. A. M., Sigulinsky, C. L., Dedek, K., Lin, Y.-P., Echeverry, F. A., Hoff, H., Pereda, A. E., Jones, B. W., Ribelayga, C. P., Ebnet, K., Matsuura, K., & O'Brien, J. (2026). Uncovering the electrical synapse proteome in retinal neurons via in vivo proximity labeling. eLife, 14, RP105935. https://
BibTeX
@article{tetenborg2026un
author = {Tetenborg, Stephan and Shihabeddin, Eyad and Kumar, Elizebeth Olive Akansha Manoj and Sigulinsky, Crystal L and Dedek, Karin and Lin, Ya-Ping and Echeverry, Fabio A and Hoff, Hannah and Pereda, Alberto E and Jones, Bryan W and Ribelayga, Christophe P and Ebnet, Klaus and Matsuura, Ken and O'Brien, John},
title = {{Uncovering the electrical synapse proteome in retinal neurons via in vivo proximity labeling}},
journal = {eLife},
year = {2026},
month = may,
volume = {14},
pages = {RP105935},
publisher = {eLife Sciences Publications, Ltd},
issn = {2050-084X},
doi = {10.7554/
url = {https://
pmid = {42159345},
pmcid = {PMC13189625}
}
RIS
TY - JOUR
AU - Tetenborg, Stephan
AU - Shihabeddin, Eyad
AU - Kumar, Elizebeth Olive Akansha Manoj
AU - Sigulinsky, Crystal L
AU - Dedek, Karin
AU - Lin, Ya-Ping
AU - Echeverry, Fabio A
AU - Hoff, Hannah
AU - Pereda, Alberto E
AU - Jones, Bryan W
AU - Ribelayga, Christophe P
AU - Ebnet, Klaus
AU - Matsuura, Ken
AU - O'Brien, John
TI - Uncovering the electrical synapse proteome in retinal neurons via in vivo proximity labeling
T2 - eLife
J2 - eLife
PY - 2026
DA - 2026/
VL - 14
SP - RP105935
SN - 2050-084X
PB - eLife Sciences Publications, Ltd
DO - 10.7554/
UR - https://
LA - en
ER -
CSL-JSON
{
"id": "10.7554/
"type": "article-journal",
"title": "Uncovering the electrical synapse proteome in retinal neurons via in vivo proximity labeling",
"container-title": "eLife",
"author": [
{
"family": "Tetenborg",
"given": "Stephan"
},
{
"family": "Shihabeddin",
"given": "Eyad"
},
{
"family": "Kumar",
"given": "Elizebeth Olive Akansha Manoj"
},
{
"family": "Sigulinsky",
"given": "Crystal L"
},
{
"family": "Dedek",
"given": "Karin"
},
{
"family": "Lin",
"given": "Ya-Ping"
},
{
"family": "Echeverry",
"given": "Fabio A"
},
{
"family": "Hoff",
"given": "Hannah"
},
{
"family": "Pereda",
"given": "Alberto E"
},
{
"family": "Jones",
"given": "Bryan W"
},
{
"family": "Ribelayga",
"given": "Christophe P"
},
{
"family": "Ebnet",
"given": "Klaus"
},
{
"family": "Matsuura",
"given": "Ken"
},
{
"family": "O'Brien",
"given": "John"
}
],
"container-title-short":
"volume": "14",
"page": "RP105935",
"DOI": "10.7554/
"PMID": "42159345",
"PMCID": "PMC13189625",
"ISSN": "2050-084X",
"publisher": "eLife Sciences Publications, Ltd",
"URL": "https://
"language": "en",
"issued": {
"date-parts": [
[
2026,
5,
20
]
]
}
}
Similar papers
The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.
- [1] doi:10.1038/s41586-026-10501-y [code]
- Long-term editing of brain circuits using an engineered electrical synapse.Journal: NatureIn common: mouse, cellular / molecular, 5 references
- [2] doi:10.1002/ejp.70277 [code]
- Proximity Labelling Reveals the Compartmental Proteome of Murine Sensory Neurons.Journal: European journal of pain (London, England)In common: genetics / omics, mouse, cellular / molecular, 4 references
- [3] doi:10.1126/sciadv.aeg3223 [code]
- The extreme diversity of retinal amacrine cells has deep evolutionary roots.Journal: Science advancesIn common: genetics / omics, cellular / molecular, 4 references
- [4] doi:10.1038/s42003-026-10464-w [code]
- Quantifying electrostatic control of docking and binding energetics in functional Cx36 gap junctions.Journal: Communications biologyIn common: cellular / molecular, 3 references
- [5] doi:10.1038/s41398-026-04018-1
- Loss of connexin 36 elicits abnormalities in thalamocortical network activity relevant to neuropsychiatric disorders.Journal: Translational psychiatryIn common: mouse, 3 references
- [6] doi:10.1038/s41467-026-71919-6 [code]
- Suppression of astrocyte BMP signaling improves molecular signatures and functional deficits in a fragile X syndrome mouse model.Journal: Nature communicationsIn common: genetics / omics, mouse, cellular / molecular, 3 references
- [7] doi:10.1038/s41467-026-76587-0 [code]
- Uncovering the signaling networks of disseminated glioblastoma cells in vivo with INSIGHT.Journal: Nature communicationsIn common: genetics / omics, mouse, cellular / molecular, 3 references
- [8] doi:10.7554/elife.103046 [code]
- Dichotomy between extracellular signatures of active dendritic chemical synapses and gap junctions.Journal: eLifeIn common: cellular / molecular, 2 references
- [9] doi:10.1126/sciadv.aed5548 [code]
- In situ proteomics unveils specialized domains for extrasynaptic signaling on neuronal cilia.Journal: Science advancesIn common: genetics / omics, mouse, cellular / molecular, 2 references
- [10] doi:10.1038/s41467-026-76132-z [code]
- ATP13A4 gates extracellular polyamine levels to control excitatory synaptogenesis.Journal: Nature communicationsIn common: mouse, 2 references
Contribute
The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.
Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.
Claim this paper
Correct its record
Say what each link of this record is, remove the ones that are not the paper's, add the ones that are missing. The correction becomes a new version of the record, in its Versions section.
Request its removal
To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).
Discussion, reproductions, activity
Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.
Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.
Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.