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Cited by 129Slime Mold and Myxomycetes ResearchProtein Kinase Regulation and GTPase SignalingCellular transport and secretion

G Protein β Subunit–null Mutants Are Impaired in Phagocytosis and Chemotaxis Due to Inappropriate Regulation of the Actin Cytoskeleton

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Peracino, Barbara, Borleis, Jane, Jin, Tian, Westphal, Monika, Schwartz, Jean-Marc, Wu, Lijun, Bracco, Enrico, Gerisch, Günther +2 more·1998·The Journal of Cell Biology
DOI 10.1083/jcb.141.7.1529PMC PMC2133009
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Abstract

Chemotaxis and phagocytosis are basically similar in cells of the immune system and in Dictyostelium amebae. Deletion of the unique G protein β subunit in D. discoideum impaired phagocytosis but had little effect on fluid-phase endocytosis, cytokinesis, or random motility. Constitutive expression of wild-type β subunit restored phagocytosis and normal development. Chemoattractants released by cells or bacteria trigger typical transient actin polymerization responses in wild-type cells. In β subunit–null cells, and in a series of β subunit point mutants, these responses were impaired to a degree that correlated with the defect in phagocytosis. Image analysis of green fluorescent protein–actin transfected cells showed that β subunit– null cells were defective in reshaping the actin network into a phagocytic cup, and eventually a phagosome, in response to particle attachment. Our results indicate that signaling through heterotrimeric G proteins is required for regulating the actin cytoskeleton during phagocytic uptake, as previously shown for chemotaxis. Inhibitors of phospholipase C and intracellular Ca2+ mobilization inhibited phagocytosis, suggesting the possible involvement of these effectors in the process.

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  • Molecular mechanisms of phagocytosis are conserved throughout evolution.

    “Molecular mechanisms of phagocytosis are conserved throughout evolution.”

    From Genome-wide transcriptional changes induced by phagocytosis or growth on bacteria in Dictyostelium (2008) · cites this paper as [5]

    The paper’s opening passage (labeled Abstract in our copy; page unavailable) describes remarkably similar biochemical reactions and actin-based phagocytic structures in Dictyostelium and animal immune cells. That supports shared mechanisms across those groups, but the paper does not establish that molecular mechanisms of phagocytosis are conserved throughout evolution; it also frames its evolutionary inference as a suggestion. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • PI3K and PTEN, in contrast to PLC, are not essential for bacterial uptake, but pi3k1-2 null mutants are defective in phago-lysosomal maturation.

    “PI3K and PTEN, in contrast to PLC, are not essential for bacterial uptake [5,73] [Balest, unpublished results], but pi3k1-2 null mutants are defective in phago-lysosomal maturation [17,74] [Balest, unpublished results].”

    From Genome-wide transcriptional changes induced by phagocytosis or growth on bacteria in Dictyostelium (2008) · cites this paper as [5]

    In Results, “Downstream Transduction Pathways Regulating Phagocytosis” (page unavailable), PI3-kinase inhibitors did not affect phagocytosis, whereas PLC inhibitors strongly reduced it. This supports the contrast for bacterial uptake, but the paper does not establish that PTEN is dispensable; its Discussion also treats PLC’s role as preliminary rather than proving PLC essential. The phago-lysosomal maturation claim is attached to other citations in the citing sentence. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Cell signalling during phagocytosis is virtually unknown in Dictyostelium, except for the involvement of heterotrimeric G protein and PLC.

    “Cell signalling during phagocytosis is virtually unknown in Dictyostelium, except for the involvement of the heterotrimeric G protein and PLC in the process [1,5,35].”

    From Genome-wide transcriptional changes induced by phagocytosis or growth on bacteria in Dictyostelium (2008) · cites this paper as [5]

    The Abstract proposes a heterotrimeric G-protein pathway in Dictyostelium phagocytosis, but describes PLC involvement as possible rather than established. The Results section, “Downstream Transduction Pathways Regulating Phagocytosis” (page unavailable), reports inhibition by PLC inhibitors and a calcium chelator; the Discussion says further work is needed to confirm PLC’s role. Thus the paper supports limited knowledge of the pathway and G-protein involvement, but not the claim’s unqualified statement that PLC involvement is known. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Receptor clustering on the site of bacterial binding was proposed long ago to explain heterotrimeric G protein activation, which in Dictyostelium strongly stimulates phagocytosis by favouring actin recruitment to the progressing phagocytic cup.

    “Receptor clustering on the site of bacterial binding was proposed long ago to explain heterotrimeric G protein activation, which in Dictyostelium strongly stimulates phagocytosis by favouring actin recruitment to the progressing phagocytic cup [5].”

    From Genome-wide transcriptional changes induced by phagocytosis or growth on bacteria in Dictyostelium (2008) · cites this paper as [5]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

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Cites

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Cited by

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Authors
Peracino, B., Borleis, J., Jin, T., Westphal, M., Schwartz, J.-M., Wu, L., Bracco, E., Gerisch, G., Devreotes, P., & Bozzaro, S.
Affiliations
Johns Hopkins University (US)
Corresponding author
Bozzaro, Salvatore
ORCID
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
1998-06-29
Volume
141
Issue
7
Pages
1529-1537
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.141.7.1529
PMC
PMC2133009
OpenAlex
W2159113211
Cited by
129
References
2
Citations by year
2024: 2 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 2 · 2014: 7 · 2013: 6 · 2012: 4
FWCI
10.97
Type
journal article
Language
en
Open access
Locations
  • The Journal of Cell Biology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion)
Funders
National Institute of General Medical Sciences (R37GM028007, GM28007, R01GM028007)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Slime Mold and Myxomycetes Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
G protein beta subunit, phagocytosis, chemotaxis, actin cytoskeleton, Dictyostelium discoideum, heterotrimeric G proteins, phagocytic cup, phagosome formation, actin polymerization, phospholipase C, calcium mobilization, chemoattractants
MeSH terms
Actins, Animals, Cell Division, Cell Movement, Chemotactic Factors, Chemotaxis, Cytoskeleton, Dictyostelium, Escherichia coli, Phagocytosis, Pinocytosis, Salmonella, Signal Transduction, Mutagenesis, GTP-Binding Proteins

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