Evidence map›Paper›PMID 38943612›Full record

ArticleJournal of leukocyte biology2024

RhoGDI in RBL-2H3 cells acts as a negative regulator of Rho GTPase signaling to inhibit granule exocytosis.

Eric L Zhang, Jennifer Van Petten, Gary Eitzen

Abstract read
In one paragraph

Article in Journal of leukocyte biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

3 authors.

Eric L ZhangDepartment of Cell Biology, University of Alberta, Edmonton, Alberta, Canada.
Jennifer Van PettenDepartment of Cell Biology, University of Alberta, Edmonton, Alberta, Canada.
Gary EitzenDepartment of Cell Biology, University of Alberta, Edmonton, Alberta, Canada.ORCID 0000-0003-1867-1526

Funding

Alberta Graduate Excellence Scholarship from the University of Alberta RRID:SCR_019195CIHRFaculty of Medicine and Dentistry and Canada Foundation for InnovationNatural Sciences and Engineering Research Council of Canada RGPIN-2019-05466
6 · The paper itself

Abstract

Mast cells are hematopoietic-derived immune cells that possess numerous cytoplasmic granules containing immune mediators such as cytokines and histamine. Antigen stimulation triggers mast cell granule exocytosis, releasing granule contents in a process known as degranulation. We have shown that Rho GTPase signaling is an essential component of granule exocytosis, however, the proteins that regulate Rho GTPases during this process are not well defined. Here we examined the role of Rho guanine-nucleotide dissociation inhibitors (RhoGDIs) in regulating Rho GTPase signaling using RBL-2H3 cells as a mast cell model. We found that RBL-2H3 cells express two RhoGDI isoforms which are primarily localized to the cytosol. Knockdown of RhoGDI1 and RhoGDI2 greatly reduced the levels of all Rho GTPases tested: RhoA, RhoG, Rac1, Rac2, and Cdc42. The reduction in Rho GTPase levels was accompanied by an increase in their membrane-localized fraction and an elevation in the levels of active Rho GTPases. All RhoGDI knockdown strains had altered resting cell morphology, although each strain was activation competent when stimulated. Live cell imaging revealed that the RhoGDI1/2 double knockdown (DKD) strain maintained its activated state for prolonged periods of time compared to the other strains. Only the RhoGDI1/2 DKD strain showed a significant increase in granule exocytosis. Conversely, RhoGDI overexpression in RBL-2H3 cells did not noticeably affect Rho GTPases or degranulation. Based on these results, RhoGDIs act as negative regulators of Rho GTPases during mast cell degranulation, and inhibit exocytosis by sequestering Rho GTPases in the cytosol.

Indexed as

ExocytosisMast Cellsrho GTP-Binding ProteinsSignal TransductionAnimalsCell DegranulationCytoplasmic GranulesRatsrho Guanine Nucleotide Dissociation Inhibitor alpharho Guanine Nucleotide Dissociation Inhibitor betarho-Specific Guanine Nucleotide Dissociation Inhibitorsrho GTP-Binding Proteinsrho Guanine Nucleotide Dissociation Inhibitor alpharho Guanine Nucleotide Dissociation Inhibitor betarho-Specific Guanine Nucleotide Dissociation InhibitorsdegranulationFcεR1mast cellRac1RhoA

Identifiers

PMID38943612
PMCPMC11599123

What Socratic holds

Textmetadata
LicenceCC BY
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.