Evidence map›Paper›PMID 29599294›Full record

ArticleThe Journal of biological chemistry2018

Munc18-2, but not Munc18-1 or Munc18-3, controls compound and single-vesicle-regulated exocytosis in mast cells.

Berenice A Gutierrez, Miguel A Chavez, Alejandro I Rodarte, Marco A Ramos, Andrea Dominguez, Youlia Petrova, Alfredo J Davalos, Renan M Costa, Ramon Elizondo, Michael J Tuvim and 4 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.0field-weighted citation impact, top 15% 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

15 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. LRO biogenesis and function: what can we learn from mast cells?Frontiers in cell and developmental biology · 2025
    Review
  3. Article
  4. Exocytic machineries differentially control mediator release from allergen-triggered RBL-2H3 cells.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023
    Article
  5. The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Molecular Regulatory Mechanism of Exocytosis in the Salivary Glands.International journal of molecular sciences · 2018
    Review
  15. 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

14 authors at 4 institutions in 2 countries.

Berenice A GutierrezDepartment of Pulmonary Medicine, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030; Escuela de Ingeniería y Ciencias, Tecnologico de Monterrey, Monterrey NL 64849 México.
Miguel A ChavezDepartment of Pulmonary Medicine, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030; Escuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, Monterrey NL 64710 México.
Alejandro I RodarteDepartment of Pulmonary Medicine, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030; Escuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, Monterrey NL 64710 México.
Marco A RamosDepartment of Pulmonary Medicine, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030.
Andrea DominguezEscuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, Monterrey NL 64710 México.
Youlia PetrovaDepartment of Pulmonary Medicine, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030.
Alfredo J DavalosDepartment of Pulmonary Medicine, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030.
Renan M CostaGraduate School of Biomedical Sciences, Houston, Texas 77030.
Ramon ElizondoEscuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, Monterrey NL 64710 México.
Michael J TuvimDepartment of Pulmonary Medicine, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030.
Burton F DickeyDepartment of Pulmonary Medicine, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030.
Alan R BurnsCollege of Optometry, University of Houston, Houston, Texas 77204.
Ruth HeidelbergerDepartment of Neurobiology and Anatomy, McGovern Medical School, University of Texas Health Science Center, Houston, Texas 77030.
Roberto AdachiDepartment of Pulmonary Medicine, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030. Electronic address: radachi@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USTecnológico de Monterrey · MXThe University of Texas Health Science Center at Houston · USUniversity of Houston · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Research Programming ModuleP30EY007551 · NEI · UNIVERSITY OF HOUSTON · PI LAURA J. FRISHMAN · 1988 to 2026
$16.4M
Mechanisms of Neurotransmisson in Vertebrate RetinaR01EY012128 · NEI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI HEIDELBERGER, RUTH · 2003 to 2025
$8.0M
Controlling the core airway mucin secretion machinery to prevent pathophysiologyR01HL129795 · NHLBI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DICKEY, BURTON F · 2015 to 2023
$3.8M
Mechanism and pathophysiological significance of mast cell regulated exocytosisR01AI093533 · NIAID · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ADACHI, ROBERTO · 2011 to 2015
$2.1M
MECHANISMS OF NEUROTRANSMISSION IN VERTEBRATE RETINAR29EY012128 · NEI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI HEIDELBERGER, RUTH · 1998 to 2002
$343k
NCI NIH HHS P30 CA016672NEI NIH HHS P30 EY007551NEI NIH HHS R01 EY012128NEI NIH HHS R29 EY012128NHLBI NIH HHS R01 HL129795NIAID NIH HHS R01 AI093533
6 · The paper itself

Abstract

Mast cells (MCs) play pivotal roles in many inflammatory conditions including infections, anaphylaxis, and asthma. MCs store immunoregulatory compounds in their large cytoplasmic granules and, upon stimulation, secrete them via regulated exocytosis. Exocytosis in many cells requires the participation of Munc18 proteins (also known as syntaxin-binding proteins), and we found that mature MCs express all three mammalian isoforms: Munc18-1, -2, and -3. To study their functions in MC effector responses and test the role of MC degranulation in anaphylaxis, we used conditional knockout (cKO) mice in which each Munc18 protein was deleted exclusively in MCs. Using recordings of plasma membrane capacitance for high-resolution analysis of exocytosis in individual MCs, we observed an almost complete absence of exocytosis in Munc18-2-deficient MCs but intact exocytosis in MCs lacking Munc18-1 or Munc18-3. Stereological analysis of EM images of stimulated MCs revealed that the deletion of Munc18-2 also abolishes the homotypic membrane fusion required for compound exocytosis. We confirmed the severe defect in regulated exocytosis in the absence of Munc18-2 by measuring the secretion of mediators stored in MC granules. Munc18-2 cKO mice had normal morphology, development, and distribution of their MCs, indicating that Munc18-2 is not essential for the migration, retention, and maturation of MC-committed progenitors. Despite that, we found that Munc18-2 cKO mice were significantly protected from anaphylaxis. In conclusion, MC-regulated exocytosis is required for the anaphylactic response, and Munc18-2 is the sole Munc18 isoform that mediates membrane fusion during MC degranulation.

Indexed as

AnaphylaxisAnimalsCell DegranulationExocytosisGene DeletionMast CellsMembrane FusionMice, Inbred C57BLMice, KnockoutMicroscopy, ElectronMunc18 ProteinsPatch-Clamp TechniquesMunc18 ProteinsStxbp1 protein, mouseStxbp2 protein, mouseStxbp3 protein, mouseallergyanaphylaxiselectrophysiologyexocytosismast cellMunc18patch clampsecretionSNARE proteinssyntaxin-binding protein

Identifiers

PMID29599294
PMCPMC5950006
OpenAlexW2795210131

What Socratic 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 Socratic graph.