Evidence map›Paper›PMID 25352602›Full record

ArticleThe Journal of biological chemistry2014

Calsyntenin-3 molecular architecture and interaction with neurexin 1α.

Zhuoyang Lu, Yun Wang, Fang Chen, Huimin Tong, M V V V Sekhar Reddy, Lin Luo, Suchithra Seshadrinathan, Lei Zhang, Luis Marcelo F Holthauzen, Ann Marie Craig and 2 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

41 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
  2. Calsyntenin-3 suppresses inflammation via inhibition of TLR N-glycosylation and membrane localization.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  14. Neurexins and their ligands at inhibitory synapses.Frontiers in synaptic neuroscience · 2022
    Review
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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

12 authors at 4 institutions in 3 countries.

Zhuoyang Luthe Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720, the School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
Yun Wangthe University of Michigan, Ann Arbor, Michigan 48109.
Fang Chenthe University of Michigan, Ann Arbor, Michigan 48109.
Huimin Tongthe Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720.
M V V V Sekhar ReddyFrom the Department of Pharmacology and Toxicology and.
Lin Luothe Department of Psychiatry, University of British Columbia, Vancouver V6T 2A1, Canada, and.
Suchithra SeshadrinathanFrom the Department of Pharmacology and Toxicology and.
Lei Zhangthe Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720.
Luis Marcelo F Holthauzenthe Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston Texas 77555.
Ann Marie Craigthe Department of Psychiatry, University of British Columbia, Vancouver V6T 2A1, Canada, and.
Gang Renthe Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720, gren@lbl.gov.
Gabby RudenkoFrom the Department of Pharmacology and Toxicology and the Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston Texas 77555, garudenk@utmb.edu.
Lawrence Berkeley National Laboratory · USThe University of Texas Medical Branch at Galveston · USUniversity of British Columbia · CAUniversity of Michigan · US

Funding

Synaptic Organizers: Dynamic Regulation of Trans-synaptic BridgesR01MH077303 · NIMH · UNIVERSITY OF TEXAS MED BR GALVESTON · PI Gabrielle Rudenko · 2006 to 2026
$8.2M
Structure-Function Relationship Studies of the Plasma Lipid Transfer Proteins CETP and PLTPR01HL115153 · NHLBI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI REN, GANG · 2012 to 2021
$3.9M
Mechanisms of Central Neuron SynaptogenesisR01MH070860 · NIMH · UNIVERSITY OF BRITISH COLUMBIA · PI CRAIG, ANN M · 2005 to 2015
$2.3M
Lipoprotein Structure and Function by Individual Particle Electron TomographyR01GM104427 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI REN, GANG · 2013 to 2016
$1.3M
NHLBI NIH HHS R01 HL115153NIGMS NIH HHS R01 GM104427NIMH NIH HHS R01 MH070860NIMH NIH HHS R01MH070860NIMH NIH HHS R01 MH077303NIMH NIH HHS R01MH077303
6 · The paper itself

Abstract

Calsyntenin 3 (Cstn3 or Clstn3), a recently identified synaptic organizer, promotes the development of synapses. Cstn3 localizes to the postsynaptic membrane and triggers presynaptic differentiation. Calsyntenin members play an evolutionarily conserved role in memory and learning. Cstn3 was recently shown in cell-based assays to interact with neurexin 1α (n1α), a synaptic organizer that is implicated in neuropsychiatric disease. Interaction would permit Cstn3 and n1α to form a trans-synaptic complex and promote synaptic differentiation. However, it is contentious whether Cstn3 binds n1α directly. To understand the structure and function of Cstn3, we determined its architecture by electron microscopy and delineated the interaction between Cstn3 and n1α biochemically and biophysically. We show that Cstn3 ectodomains form monomers as well as tetramers that are stabilized by disulfide bonds and Ca(2+), and both are probably flexible in solution. We show further that the extracellular domains of Cstn3 and n1α interact directly and that both Cstn3 monomers and tetramers bind n1α with nanomolar affinity. The interaction is promoted by Ca(2+) and requires minimally the LNS domain of Cstn3. Furthermore, Cstn3 uses a fundamentally different mechanism to bind n1α compared with other neurexin partners, such as the synaptic organizer neuroligin 2, because Cstn3 does not strictly require the sixth LNS domain of n1α. Our structural data suggest how Cstn3 as a synaptic organizer on the postsynaptic membrane, particularly in tetrameric form, may assemble radially symmetric trans-synaptic bridges with the presynaptic synaptic organizer n1α to recruit and spatially organize proteins into networks essential for synaptic function.

Indexed as

Amino Acid SequenceAnimalsCalcium-Binding ProteinsCattleExtracellular SpaceHEK293 CellsHumansMembrane ProteinsModels, MolecularMolecular Sequence DataProtein BindingProtein MultimerizationProtein Structure, QuaternaryProtein Structure, TertiaryRatsReceptors, Cell SurfaceCalcium-Binding ProteinsCLSTN3 protein, humanMembrane ProteinsNrxn1 protein, ratReceptors, Cell SurfaceCalsynteninsCell AdhesionCell Surface ReceptorNeurexinsNeuropsychiatric DisordersProtein-Protein InteractionSingle-particle AnalysisSynapseSynaptic Organizers

Identifiers

PMID25352602
PMCPMC4263861
OpenAlexW2005128600

What OpenQuestion holds

Textmetadata
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.