Distinct Roles of PI(3,4,5)P 3 during Chemoattractant Signaling in Dictyostelium : A Quantitative In Vivo Analysis by Inhibition of PI3-Kinase
Open accessAbstract
The role of PI(3,4,5)P 3 in Dictyostelium signal transduction and chemotaxis was investigated using the PI3-kinase inhibitor LY294002 and pi3k-null cells. The increase of PI(3,4,5)P 3 levels after stimulation with the chemoattractant cAMP was blocked >95% by 60 μM LY294002 with half-maximal effect at 5 μM. This correlated well with the inhibition of the membrane translocation of the PH-domain protein, PHcracGFP. LY294002 did not reduce cAMP-mediated cGMP production, but significantly reduced the cAMP response up to 75% in wild type and completely in pi3k-null cells. LY294002-treated cells were round, not elongated as control cells. Interestingly, cAMP induced a time and dose-dependent recovery of cell elongation. These elongated LY294002-treated wild-type and pi3k-null cells exhibited chemotactic orientation toward cAMP that is statistically identical to chemotactic orientation of control cells. In control cells, PHcrac-GFP and F-actin colocalize upon cAMP stimulation. However, inhibition of PI3-kinases does not affect the first phase of the actin polymerization at a wide range of chemoattractant concentrations. Our data show that severe inhibition of cAMP-mediated PI(3,4,5)P 3 accumulation leads to inhibition of cAMP relay, cell elongation and cell aggregation, but has no detectable effect on chemotactic orientation, provided that cAMP had sufficient time to induce cell elongation.
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In Dictyostelium, cells with cPI3K genetically eliminated still migrate but are substantially retarded.
“However, studies conducted in the model organism Dictyostelium, where cPI3K was genetically eliminated, revealed that cells still migrate but are substantially retarded [53,54].”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [53]
The Effect of LY294002 on Chemotaxis section reports that pi3k1/2-null cells still migrate, but their speed without inhibitor is not very different from wild-type cells. The substantial slowing occurs after LY294002 treatment, not from genetic disruption alone; the paper also specifies that only two of six potential PI3-kinase genes were disrupted. Page numbers were not available in our copy. (LLM, conf=0.89)
Experimental — accuracy not yet measuredPIP3 serves as a crucial second messenger in cell migration.
“PIP3 serves as a crucial second messenger in cellular processes, particularly in cell migration [53].”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [53]
The section “The Function of PI(3,4,5)P3 in Cell Polarity and Chemotaxis” describes PI3K signaling as crucial to Dictyostelium chemotactic movement, particularly cell speed and polarity. But the Introduction says that severe reduction of PIP3 has no strong effect on chemotaxis once cells elongate. The source therefore supports a role for PIP3 in migration-related processes, not the unqualified claim that PIP3 itself is crucial for cell migration generally. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIPMK plays a crucial role in migration.
“It plays a crucial role in cell proliferation [34], metabolism [58], autophagy [14,64], and migration [34,53,54].”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [53]
The section ‘The Function of PI(3,4,5)P3 in Cell Polarity and Chemotaxis’ describes a crucial role for PI3K signaling in Dictyostelium chemotaxis, not for IPMK. Searches for IPMK and inositol polyphosphate multikinase found no passage in our copy addressing IPMK’s role in migration. (LLM, conf=0.76)
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Research works printed but not linked: 3
- Janetopoulos, C., Ma, L., Devreotes, P. N., and Iglesias, P. A. (2004). Chemoattractant-induced phosphatidylinositol 3,4,5-trisphosphate accumulation is spatially amplified and adapts, independent of the actin cytoskeleton. Proc. Natl. Acad. Sci. USA 101 , 8951-8956.
- Mato, J. M., Losada, A., Nanjundiah, V., and Konijn, T. M. (1975). Signal input for a chemotactic response in the cellular slime mold Dictyostelium discoideum. Proc. Natl. Acad. Sci. USA 72 , 4991-4993.
- Potma, E., de Boeij, W. P., van Haastert, P. J., and Wiersma, D. A. (2001). Real-time visualization of intracellular hydrodynamics in single living cells. Proc. Natl. Acad. Sci. USA 98 , 1577-1582.
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From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease
Mishra, S. H., Chatterjee, S., Viera-Preval, L., & Guha, P. (2025) · Biomolecules · doi:10.3390/biom15091266 · Cited by 1 · see citing works
“It plays a crucial role in cell proliferation [34], metabolism [58], autophagy [14,64], and migration [34,53,54].”
- Authors
- Loovers, H. M., Postma, M., Keizer-Gunnink, I., Huang, Y. E., Devreotes, P. N., & van Haastert, P. J. M.
- Affiliations
- University of Groningen (NL)
- Department of Molecular Cell Biology, University of Groningen, 9751NN Haren, The Netherlands
- Johns Hopkins University (US)
- Venue
- Molecular Biology of the Cell
- Published
- 2006-04
- Volume
- 17
- Issue
- 4
- Pages
- 1503-1513
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC1415331
- OpenAlex
- W2095927835
- Cited by
- 104
- References
- 0
- Citations by year
- 2025: 3 · 2023: 3 · 2022: 2 · 2021: 4 · 2019: 2 · 2018: 4 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 7 · 2012: 7
- FWCI
- 6.52
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular Biology of the Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by-nc-sa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- National Institute of General Medical Sciences (R01GM028007)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Physical Sciences › Engineering › Biomedical Engineering › Slime Mold and Myxomycetes Research
- Keywords
- PI3-kinase, Dictyostelium, cAMP signaling, chemotaxis, cell elongation, cell aggregation, LY294002, cyclic GMP, actin polymerization, signal transduction
- MeSH terms
- Phosphoinositide-3 Kinase Inhibitors, Actins, Cyclic AMP, Animals, Cell Aggregation, Chemotactic Factors, Chemotaxis, Chromones, Dictyostelium, Enzyme Inhibitors, Morpholines, Phosphatidylinositols, Thiazoles, Signal Transduction, Protozoan Proteins, Cell Polarity, Bridged Bicyclo Compounds, Heterocyclic, Phosphatidylinositol 3-Kinases, Cell Shape, Cell Enlargement, Green Fluorescent Proteins, Thiazolidines
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