Evidence map›Paper›PMID 31262725›Full record

ArticleThe Journal of cell biology2019

Synaptic neurexin-1 assembles into dynamically regulated active zone nanoclusters.

Justin H Trotter, Junjie Hao, Stephan Maxeiner, Theodoros Tsetsenis, Zhihui Liu, Xiaowei Zhuang, Thomas C Südhof

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in The Journal of cell biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
7.1field-weighted citation impact, top 2% 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

63 citing papers in PubMed, 117 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Alpha-neurexins in health and disease.Frontiers in molecular neuroscience · 2025
    Review
  17. Article
  18. Non-canonical function of ADAM10 in presynaptic plasticity.Cellular and molecular life sciences : CMLS · 2024
    Article
  19. Article
  20. Article

3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Justin H Trotter *Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA.
Junjie Hao *Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA.
Stephan MaxeinerDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA.ORCID 0000-0002-4472-695X
Theodoros TsetsenisDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA.
Zhihui LiuDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA.
Xiaowei ZhuangDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA zhuang@chemistry.harvard.edu.
Thomas C SüdhofDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA tcs1@stanford.edu.ORCID 0000-0003-3361-9275
Howard Hughes Medical Institute · US

Funding

Generation of novel cell type specific mouse genetic toolsU19MH114830 · NIMH · ALLEN INSTITUTE · PI NGAI, JOHN J. · 2017 to 2021
$64.7M
FUNCTION OF NEUREXINSR37MH052804 · NIMH · UT SOUTHWESTERN MEDICAL CENTER · PI SUDHOF, THOMAS C. · 2000 to 2019
$9.3M
Working Memory in Parkinson Disease: A Cognitive & Systems Neuroscience ApproachP50AG047366 · NIA · STANFORD UNIVERSITY · PI PERIYAKOIL, VYJEYANTHI S · 2015 to 2019
$7.9M
Function of NeurexinsR01MH052804 · NIMH · UNIVERSITY OF TEXAS SW MED CTR/DALLAS · PI SUDHOF, THOMAS C. · 1994 to 2024
$3.7M
Illuminating molecular mechanisms of cellular functions by single-molecule and super-resolution imagingR35GM122487 · NIGMS · HARVARD UNIVERSITY · PI ZHUANG, XIAOWEI · 2017 to 2021
$2.1M
Regulation of Synapse Formation and Function by Neurexin-1 ProteolysisF32MH105040 · NIMH · STANFORD UNIVERSITY · PI TROTTER, JUSTIN HOWARD · 2014 to 2016
$158k
NIA NIH HHS P50 AG047366NIGMS NIH HHS R35 GM122487NIMH NIH HHS F32 MH105040NIMH NIH HHS R01 MH052804NIMH NIH HHS R37 MH052804NIMH NIH HHS U19 MH114830
6 · The paper itself

Abstract

Neurexins are well-characterized presynaptic cell adhesion molecules that engage multifarious postsynaptic ligands and organize diverse synapse properties. However, the precise synaptic localization of neurexins remains enigmatic. Using super-resolution microscopy, we demonstrate that neurexin-1 forms discrete nanoclusters at excitatory synapses, revealing a novel organizational feature of synaptic architecture. Synapses generally contain a single nanocluster that comprises more than four neurexin-1 molecules and that also includes neurexin-2 and/or neurexin-3 isoforms. Moreover, we find that neurexin-1 is physiologically cleaved by ADAM10 similar to its ligand neuroligin-1, with ∼4-6% of neurexin-1 and ∼2-3% of neuroligin-1 present in the adult brain as soluble ectodomain proteins. Blocking ADAM10-mediated neurexin-1 cleavage dramatically increased the synaptic neurexin-1 content, thereby elevating the percentage of Homer1(+) excitatory synapses containing neurexin-1 nanoclusters from 40-50% to ∼80%, and doubling the number of neurexin-1 molecules per nanocluster. Taken together, our results reveal an unexpected nanodomain organization of synapses in which neurexin-1 is assembled into discrete presynaptic nanoclusters that are dynamically regulated via ectodomain cleavage.

Indexed as

ADAM10 ProteinAnimalsCalcium-Binding ProteinsCell Adhesion Molecules, NeuronalCells, CulturedEpitopesHEK293 CellsHumansMice, Inbred C57BLNanoparticlesNeural Cell Adhesion MoleculesNeuronsPresynaptic TerminalsProtein IsoformsProteolysisSynapsesADAM10 ProteinCalcium-Binding ProteinsCell Adhesion Molecules, NeuronalEpitopesNeural Cell Adhesion Moleculesneuroligin 1Nrxn1 protein, mouseProtein Isoforms

Identifiers

PMID31262725
PMCPMC6683742
OpenAlexW2954604694

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.