Evidence map›Paper›PMID 24356451›Full record

ArticleMolecular biology of the cell2014

CAPS and Munc13 utilize distinct PIP2-linked mechanisms to promote vesicle exocytosis.

Greg Kabachinski, Masaki Yamaga, D Michelle Kielar-Grevstad, Stephen Bruinsma, Thomas F J Martin

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
2.9field-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

47 citing papers in PubMed, 70 citations in OpenAlex.

  1. Review
  2. Munc13 serves as a molecular filter for SNARE sorting and assembly in active zone condensates.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Article
  5. PI(4,5)PBiochimica et biophysica acta. Molecular and cell biology of lipids · 2025
    Review
  6. GABAProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  7. Review
  8. CaAdvances in experimental medicine and biology · 2023
    Article
  9. PI(4,5)P2: signaling the plasma membrane.The Biochemical journal · 2022
    Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Munc13-1 is a CaNeuron · 2021
    Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Phosphatidylinositol 4,5-bisphosphate in the Control of Membrane Trafficking.International journal of biological sciences · 2020
    Review
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

5 authors at 1 institution in 1 country.

Greg KabachinskiDepartment of Biochemistry, University of Wisconsin, Madison, WI 53706.
Masaki Yamaga
D Michelle Kielar-Grevstad
Stephen Bruinsma
Thomas F J Martin
University of Wisconsin–Madison · US

Funding

THE MECHANISM OF ACTION OF THYROTROPIN-RELEASING HORMONER01DK025861 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI MARTIN, THOMAS F. J. · 1986 to 2024
$5.6M
CA++ REGULATION OF SECRETION IN NEUROENDOCRINE CELLSR01DK040428 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI MARTIN, THOMAS F. J. · 1988 to 2015
$4.8M
THE MECHANISM OF ACTION OF THYROTROPIN-RELEASING HORMONER37DK025861 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI MARTIN, THOMAS F. J. · 1991 to 2008
$3.3M
Calcium Regulation of Secretion in Neuroendocrine CellsR01GM119158 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI MARTIN, THOMAS F. J. · 2016 to 2019
$1.3M
NIDDK NIH HHS DK025861NIDDK NIH HHS DK040428NIDDK NIH HHS R01 DK025861NIDDK NIH HHS R01 DK040428NIDDK NIH HHS R37 DK025861NIGMS NIH HHS R01 GM119158
6 · The paper itself

Abstract

Phosphoinositides provide compartment-specific signals for membrane trafficking. Plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2) is required for Ca(2+)-triggered vesicle exocytosis, but whether vesicles fuse into PIP2-rich membrane domains in live cells and whether PIP2 is metabolized during Ca(2+)-triggered fusion were unknown. Ca(2+)-dependent activator protein in secretion 1 (CAPS-1; CADPS/UNC31) and ubMunc13-2 (UNC13B) are PIP2-binding proteins required for Ca(2+)-triggered vesicle exocytosis in neuroendocrine PC12 cells. These proteins are likely effectors for PIP2, but their localization during exocytosis had not been determined. Using total internal reflection fluorescence microscopy in live cells, we identify PIP2-rich membrane domains at sites of vesicle fusion. CAPS is found to reside on vesicles but depends on plasma membrane PIP2 for its activity. Munc13 is cytoplasmic, but Ca(2+)-dependent translocation to PIP2-rich plasma membrane domains is required for its activity. The results reveal that vesicle fusion into PIP2-rich membrane domains is facilitated by sequential PIP2-dependent activation of CAPS and PIP2-dependent recruitment of Munc13. PIP2 hydrolysis only occurs under strong Ca(2+) influx conditions sufficient to activate phospholipase Cη2 (PLCη2). Such conditions reduce CAPS activity and enhance Munc13 activity, establishing PLCη2 as a Ca(2+)-dependent modulator of exocytosis. These studies provide a direct view of the spatial distribution of PIP2 linked to vesicle exocytosis via regulation of lipid-dependent protein effectors CAPS and Munc13.

Indexed as

Amino Acid SequenceAnimalsBiological TransportCalciumCalcium-Binding ProteinsCell MembraneCytoplasmExocytosisGene Expression RegulationIsoenzymesMicroscopy, VideoModels, MolecularMolecular Sequence DataNerve Tissue ProteinsPC12 CellsPhosphatidylinositol 4,5-DiphosphateCadps protein, ratCalciumCalcium-Binding ProteinsIsoenzymesNerve Tissue ProteinsPhosphatidylinositol 4,5-DiphosphatePhosphoinositide Phospholipase CUnc13b protein, rat

Identifiers

PMID24356451
PMCPMC3923642
OpenAlexW2099433102

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.