Evidence map›Paper›PMID 40126693›Full record

ArticleCellular and molecular life sciences : CMLS2025

PI(3,4,5)P3-mediated Cdc42 activation regulates macrophage podosome assembly.

Yaoyue Qi, Cheng-Han Yu

Abstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. 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

2 authors.

Yaoyue QiSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
Cheng-Han YuSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong. chyu1@hku.hk.ORCID http://orcid.org/0000-0002-8821-8877

Funding

Research Grants Council, University Grants Committee CRF C7070-22EFResearch Grants Council, University Grants Committee GRF 17121022
6 · The paper itself

Abstract

Podosomes are adhesion structures with densely-polymerized F-actin. While PI(3,4,5)P3 and Cdc42-GTP are known factors to trigger WASP-mediated actin polymerization at the macrophage podosome, their causal mechanism to activate WASP remains unclear. Here, we demonstrate that spatially elevated Cdc42-GTP is a downstream effector of local PI(3,4,5)P3 production at the podosome. We further examine the expression and distribution of 19 Cdc42 guanine exchange factors (GEFs) and identify VAV1 as the key PI(3,4,5)P3-dependent Cdc42 GEF. VAV1 is spatially enriched at the macrophage podosome, and the association of VAV1 with the membrane plays a critical role in upregulating its GEF activity. Reintroduction of wildtype VAV1, rather than the PI(3,4,5)P3-binding deficient or catalytically dead mutants restores the matrix degradation and chemotactic migration of VAV1-knockdown macrophage. Thus, the biogenesis of PI(3,4,5)P3 acts as an upstream signal to locally recruit VAV1 and in turn triggers the guanine nucleotide exchange of Cdc42. Elevated levels of Cdc42-GTP then promote WASP-mediated podosome assembly and macrophage chemotaxis.

Indexed as

cdc42 GTP-Binding ProteinMacrophagesPhosphatidylinositol PhosphatesPodosomesActinsAnimalsGuanine Nucleotide Exchange FactorsHumansMiceProto-Oncogene Proteins c-vavRAW 264.7 CellsActinscdc42 GTP-Binding ProteinGuanine Nucleotide Exchange Factorsphosphatidylinositol 3,4,5-triphosphatePhosphatidylinositol PhosphatesProto-Oncogene Proteins c-vavVav1 protein, mouseMacrophage migrationPhosphoinositideVAV1WASP

Identifiers

PMID40126693
PMCPMC11933580

What OpenQuestion holds

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Registered trials

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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.