Evidence map›Paper›PMID 27022630›Full record

ArticleeNeuro

Rab3-GEF Controls Active Zone Development at the Drosophila Neuromuscular Junction.

Haneui Bae, Shirui Chen, John P Roche, Minrong Ai, Chunlai Wu, Aaron Diantonio, Ethan R Graf

Open access · goldAbstract read
In one paragraph

Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.5field-weighted citation impact, top 20% of its field
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

13 citing papers in PubMed, 18 citations in OpenAlex.

  1. Disruption of a selective vesicle pool upon retrograde amnesia dissociates memory at presynaptic terminals.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  5. Muscle-fiber specific genetic manipulation ofFrontiers in physiology · 2024
    Article
  6. Article
  7. Changes in Presynaptic Gene Expression during Homeostatic Compensation at a Central Synapse.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. HumanNeural plasticity · 2017
    Article
  13. Article
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

7 authors at 3 institutions in 1 country.

Haneui BaeDepartment of Biology and Neuroscience Program, Amherst College , Amherst, Massachusetts 01002.
Shirui ChenDepartment of Biology and Neuroscience Program, Amherst College , Amherst, Massachusetts 01002.
John P RocheDepartment of Biology and Neuroscience Program, Amherst College , Amherst, Massachusetts 01002.
Minrong AiDepartment of Developmental Biology, Hope Center for Neurological Disorders, Washington University School of Medicine , St Louis, Missouri 63110.
Chunlai WuDepartment of Cell Biology and Anatomy, Neuroscience Center of Excellence , Louisiana State University Health Sciences Center , New Orleans, Louisiana 70112.
Aaron DiantonioDepartment of Developmental Biology, Hope Center for Neurological Disorders, Washington University School of Medicine , St Louis, Missouri 63110.ORCID 0000-0002-7262-0968
Ethan R GrafDepartment of Biology and Neuroscience Program, Amherst College , Amherst, Massachusetts 01002.ORCID 0000-0002-1791-2706
Amherst College · USHope Center for Neurological Disorders · USLouisiana State University Health Sciences Center New Orleans · US

Funding

MOLECULAR PATHWAYS REGULATING SYNAPTIC GROWTHR01DA020812 · NIDA · WASHINGTON UNIVERSITY · PI DIANTONIO, AARON · 2007 to 2016
$3.3M
Wrd-specific PP2A substrates that regulate AZ stabilityR21NS091892 · NINDS · LSU HEALTH SCIENCES CENTER · PI WU, CHUNLAI · 2015 to 2016
$402k
Molecular Mechanisms of Active Zone Formation at Drosophila SynapsesR15NS087601 · NINDS · AMHERST COLLEGE · PI GRAF, ETHAN R · 2014 to 2014
$372k
NIDA NIH HHS DA020812NIDA NIH HHS R01 DA020812NINDS NIH HHS NS087601NINDS NIH HHS R15 NS087601NINDS NIH HHS R21 NS091892
6 · The paper itself

Abstract

Synaptic signaling involves the release of neurotransmitter from presynaptic active zones (AZs). Proteins that regulate vesicle exocytosis cluster at AZs, composing the cytomatrix at the active zone (CAZ). At the Drosophila neuromuscular junction (NMJ), the small GTPase Rab3 controls the distribution of CAZ proteins across release sites, thereby regulating the efficacy of individual AZs. Here we identify Rab3-GEF as a second protein that acts in conjunction with Rab3 to control AZ protein composition. At rab3-GEF mutant NMJs, Bruchpilot (Brp) and Ca(2+) channels are enriched at a subset of AZs, leaving the remaining sites devoid of key CAZ components in a manner that is indistinguishable from rab3 mutant NMJs. As the Drosophila homologue of mammalian DENN/MADD and Caenorhabditis elegans AEX-3, Rab3-GEF is a guanine nucleotide exchange factor (GEF) for Rab3 that stimulates GDP to GTP exchange. Mechanistic studies reveal that although Rab3 and Rab3-GEF act within the same mechanism to control AZ development, Rab3-GEF is involved in multiple roles. We show that Rab3-GEF is required for transport of Rab3. However, the synaptic phenotype in the rab3-GEF mutant cannot be fully explained by defective transport and loss of GEF activity. A transgenically expressed GTP-locked variant of Rab3 accumulates at the NMJ at wild-type levels and fully rescues the rab3 mutant but is unable to rescue the rab3-GEF mutant. Our results suggest that although Rab3-GEF acts upstream of Rab3 to control Rab3 localization and likely GTP-binding, it also acts downstream to regulate CAZ development, potentially as a Rab3 effector at the synapse.

Indexed as

Action PotentialsAnalysis of VarianceAnimalsAnimals, Genetically ModifiedDrosophilaDrosophila ProteinsGene Expression Regulation, DevelopmentalMicroscopy, ConfocalMutationNeuromuscular JunctionNeuronsPatch-Clamp TechniquesPresynaptic Terminalsrab3 GTP-Binding ProteinsBRP protein, DrosophilaDrosophila Proteinsrab3 GTP-Binding ProteinsActive ZoneDrosophilaNeuromuscular JunctionRab3Synapse

Identifiers

PMID27022630
PMCPMC4791486
OpenAlexW2294079997

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.