Evidence map›Paper›PMID 39974889›Full record

ArticlebioRxiv : the preprint server for biology2025

A toolbox for ablating excitatory and inhibitory synapses.

Aida Bareghamyan, Changfeng Deng, Sarah Daoudi, Shubash C Yadav, Xiaocen Lu, Wei Zhang, Robert E Campbell, Richard H Kramer, David M Chenoweth, Don B Arnold

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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

5 · Who and what money

Authors and funding

10 authors.

Aida BareghamyanDepartment of Biology, Division of Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.
Changfeng DengDepartment of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0001-9138-0851
Sarah DaoudiDepartment of Biology, Division of Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.ORCID 0009-0009-5159-0729
Shubash C YadavDepartment of Molecular and Cell Biology, University of California, Berkeley, California, 94720, USA.
Xiaocen LuDepartment of Chemistry, Faculty of Science, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada.ORCID 0000-0002-8269-3837
Wei ZhangDepartment of Chemistry, Faculty of Science, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada.
Robert E CampbellDepartment of Chemistry, Faculty of Science, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada.
Richard H KramerDepartment of Molecular and Cell Biology, University of California, Berkeley, California, 94720, USA.ORCID 0000-0002-8755-9389
David M ChenowethDepartment of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-0819-4669
Don B ArnoldDepartment of Biology, Division of Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.ORCID 0000-0001-7378-1440

Funding

Photoactivatable systems for controlling transcription and ablating synapses.R01NS115610 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ARNOLD, DONALD B · 2020 to 2020
$2.1M
NINDS NIH HHS R01 NS115610
6 · The paper itself

Abstract

Recombinant optogenetic and chemogenetic proteins are potent tools for manipulating neuronal activity and controlling neural circuit function. However, there are few analogous tools for manipulating the structure of neural circuits. Here, we introduce three rationally designed genetically encoded tools that use E3 ligase-dependent mechanisms to trigger the degradation of synaptic scaffolding proteins, leading to functional ablation of synapses. First, we developed a constitutive excitatory synapse ablator, PFE3, analogous to the inhibitory synapse ablator GFE3. PFE3 targets the RING domain of the E3 ligase Mdm2 and the proteasome-interacting region of Protocadherin 10 to the scaffolding protein PSD-95, leading to efficient ablation of excitatory synapses. In addition, we developed a light-inducible version of GFE3, paGFE3, using a novel photoactivatable complex based on the photocleavable protein PhoCl2c. paGFE3 degrades Gephyrin and ablates inhibitory synapses in response to 400 nm light. Finally, we developed a chemically inducible version of GFE3, chGFE3, which degrades inhibitory synapses when combined with the bio-orthogonal dimerizer HaloTag ligand-trimethoprim. Each tool is specific, reversible, and capable of breaking neural circuits at precise locations.

Indexed as

ablationE3 ligaseGephyrinphotoactivatablePSD-95synapse

Identifiers

PMID39974889
PMCPMC11838203

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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 OpenQuestion graph.