Evidence map›Paper›PMID 25190515›Full record

ArticleThe Biochemical journal2014

Doc2b serves as a scaffolding platform for concurrent binding of multiple Munc18 isoforms in pancreatic islet β-cells.

Latha Ramalingam, Jingping Lu, Andy Hudmon, Debbie C Thurmond

Open access · greenAbstract read
In one paragraph

Article in The Biochemical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact, top 78% 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

16 citing papers in PubMed, 0 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Insulin granule biogenesis and exocytosis.Cellular and molecular life sciences : CMLS · 2021
    Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. MiR-184 expression is regulated by AMPK in pancreatic islets.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018
    Article
  13. Article
  14. Exocytosis proteins as novel targets for diabetes prevention and/or remediation?American journal of physiology. Regulatory, integrative and comparative physiology · 2017
    Review
  15. Review
  16. 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

4 authors at 1 institution in 1 country.

Latha Ramalingam*Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, U.S.A.
Jingping Lu†Department of Pediatrics, Herman B Wells Center, Indiana University School of Medicine, Indianapolis, IN 46202, U.S.A.
Andy Hudmon*Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, U.S.A.
Debbie C Thurmond
Indiana University – Purdue University Indianapolis · US

Funding

Regulation of Glucose Homeostasis by Munc18 ProteinsR01DK067912 · NIDDK · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI THURMOND, DEBBIE C · 2004 to 2023
$6.5M
Targeting PAK1 to improve functional beta-cell mass and insulin sensitivityR01DK102233 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI THURMOND, DEBBIE C, VELUTHAKAL, RAJAKRISHNAN · 2014 to 2024
$3.3M
Cdc42-regulated insulin granule exocytosisR01DK076614 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI THURMOND, DEBBIE C · 2008 to 2012
$1.6M
Regulating SNARE mechanisms to remediate glucose dyshomeostasisR56DK067912 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI FUEGER, PATRICK T., GARCIA-OCANA, ADOLFO · 2025 to 2025
$223k
NIDDK NIH HHS DK067912NIDDK NIH HHS R01 DK067912NIDDK NIH HHS R01 DK076614NIDDK NIH HHS R01 DK102233NIDDK NIH HHS R56 DK067912
6 · The paper itself

Abstract

Biphasic glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells involves soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor (SNARE) protein-regulated exocytosis. SNARE complex assembly further requires the regulatory proteins Munc18c, Munc18-1 and Doc2b. Munc18-1 and Munc18c are required for first- and second-phase GSIS respectively. These distinct Munc18-1 and Munc18c roles are related to their transient high-affinity binding with their cognate target (t-)SNAREs, Syntaxin 1A and Syntaxin 4 respectively. Doc2b is essential for both phases of GSIS, yet the molecular basis for this remains unresolved. Because Doc2b binds to Munc18-1 and Munc18c via its distinct C2A and C2B domains respectively, we hypothesized that Doc2b may provide a plasma membrane-localized scaffold/platform for transient docking of these Munc18 isoforms during GSIS. Towards this, macromolecular complexes composed of Munc18c, Doc2b and Munc18-1 were detected in β-cells. In vitro interaction assays indicated that Doc2b is required to bridge the interaction between Munc18c and Munc18-1 in the macromolecular complex; Munc18c and Munc18-1 failed to associate in the absence of Doc2b. Competition-based GST-Doc2b interaction assays revealed that Doc2b could simultaneously bind both Munc18-1 and Munc18c. Hence these data support a working model wherein Doc2b functions as a docking platform/scaffold for transient interactions with the multiple Munc18 isoforms operative in insulin release, promoting SNARE assembly.

Indexed as

AnimalsBiphasic InsulinsCalcium-Binding ProteinsExocytosisGlucoseHumansInsulin-Secreting CellsIslets of LangerhansMiceMice, KnockoutMultiprotein ComplexesMunc18 ProteinsNerve Tissue ProteinsRatsSNARE ProteinsBiphasic InsulinsCalcium-Binding ProteinsDoc2b protein, mouseGlucoseMultiprotein ComplexesMunc18 ProteinsNerve Tissue ProteinsSNARE Proteins

Identifiers

PMID25190515
PMCPMC4418448
OpenAlexW2281853912

What OpenQuestion holds

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LicenceTDM
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.