Evidence map›Paper›PMID 39605535›Full record

ArticlebioRxiv : the preprint server for biology2024

Electrical synapse molecular diversity revealed by proximity-based proteomic discovery.

Jennifer Carlisle Michel, E Anne Martin, William E Crow, Jane S Kissinger, Rachel M Lukowicz-Bedford, Max Horrocks, Tess C Branon, Alice Y Ting, Adam C Miller

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Jennifer Carlisle MichelUniversity of Oregon, Institute of Neuroscience, Eugene, OR 97405, USA.
E Anne MartinUniversity of Oregon, Institute of Neuroscience, Eugene, OR 97405, USA.
William E CrowUniversity of Oregon, Institute of Neuroscience, Eugene, OR 97405, USA.
Jane S KissingerUniversity of Oregon, Institute of Neuroscience, Eugene, OR 97405, USA.
Rachel M Lukowicz-BedfordUniversity of Oregon, Institute of Neuroscience, Eugene, OR 97405, USA.
Max HorrocksUniversity of Oregon, Institute of Neuroscience, Eugene, OR 97405, USA.
Tess C BranonDepartments of Genetics, Biology, and by courtesy, Chemistry, Stanford University, Stanford, CA, USA.
Alice Y TingDepartments of Genetics, Biology, and by courtesy, Chemistry, Stanford University, Stanford, CA, USA.
Adam C MillerUniversity of Oregon, Institute of Neuroscience, Eugene, OR 97405, USA.

Funding

Understanding the origins of rapid recurrence of pancreatic cancer after resectionP30CA069533 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Grace B Gill · 1997 to 2026
$60.5M
Proteomics CoreP30EY010572 · NEI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Kate E Keller · 1995 to 2026
$19.4M
Graduate Training in Genetics Administrative Supplement - Career Curriculum DevelopmentT32GM007413 · NIGMS · UNIVERSITY OF OREGON · PI GUILLEMIN, KAREN J · 1985 to 2022
$7.8M
Molecular Mechanisms of Electrical Synapse Formation in VivoR01NS105758 · NINDS · UNIVERSITY OF OREGON · PI Adam C Miller · 2019 to 2026
$3.7M
Graduate Training Grant in GeneticsT32GM149387 · NIGMS · UNIVERSITY OF OREGON · PI Karen J Guillemin · 2023 to 2026
$1.6M
Proteomic analysis of the electrical synapseR21NS117967 · NINDS · UNIVERSITY OF OREGON · PI MILLER, ADAM C · 2020 to 2020
$406k
Molecular Mechanisms of Synapse CoordinationF32HD102182 · NICHD · UNIVERSITY OF OREGON · PI MARTIN, ELIZABETH ANNE · 2020 to 2022
$212k
Investigating the Molecular Mechanisms that Drive Electrical Synapse DevelopmentF31NS132555 · NINDS · UNIVERSITY OF OREGON · PI KAYE, LILA E · 2023 to 2025
$143k
NCI NIH HHS P30 CA069533NEI NIH HHS P30 EY010572NICHD NIH HHS F32 HD102182NIGMS NIH HHS T32 GM007413NIGMS NIH HHS T32 GM149387NINDS NIH HHS F31 NS132555NINDS NIH HHS R01 NS105758NINDS NIH HHS R21 NS117967
6 · The paper itself

Abstract

Neuronal circuits are composed of synapses that are either chemical, where signals are transmitted via neurotransmitter release and reception, or electrical, where signals pass directly through interneuronal gap junction channels. While the molecular complexity that controls chemical synapse structure and function is well appreciated, the proteins of electrical synapses beyond the gap-junction-forming Connexins are not well defined. Yet, electrical synapses are expected to be molecularly complex beyond the gap junctions. Connexins are integral membrane proteins requiring vesicular transport and membrane insertion/retrieval to achieve function, homeostasis, and plasticity. Additionally, electron microscopy of neuronal gap junctions reveals neighboring electron dense regions termed the electrical synapse density (ESD). To reveal the molecular complexity of the electrical synapse proteome, we used proximity-dependent biotinylation (TurboID) linked to neural Connexins in zebrafish. Proteomic analysis of developing and mature nervous systems identifies hundreds of Connexin-associated proteins, with overlapping and distinct representation during development and adulthood. The identified protein classes span cell adhesion molecules, cytoplasmic scaffolds, vesicular trafficking, and proteins usually associated with the post synaptic density (PSD) of chemical synapses. Using circuits with stereotyped electrical and chemical synapses, we define molecular sub-synaptic compartments of ESD localizing proteins, we find molecular heterogeneity amongst electrical synapse populations, and we examine the synaptic intermingling of electrical and chemical synapse proteins. Taken together, these results reveal a new complexity of electrical synapse molecular diversity and highlight a novel overlap between chemical and electrical synapse proteomes. Moreover, human homologs of the electrical synapse proteins are associated with autism, epilepsy, and other neurological disorders, providing a novel framework towards understanding neuro-atypical states.

Identifiers

PMID39605535
PMCPMC11601576

What Socratic holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.