DOI: 10.1091/mbc.e02-04-0231. Agonist-induced PIP<sub>2</sub>Hydrolysis Inhibits Cortical Actin Dynamics: Regulation at a Global but not at a Micrometer Scale

Agonist-induced PIP2Hydrolysis Inhibits Cortical Actin Dynamics: Regulation at a Global but not at a Micrometer Scale

10.1091/mbc.e02-04-0231

Crossref journal-article

American Society for Cell Biology (ASCB)

Molecular Biology of the Cell (1076)

Abstract

Phosphatidylinositol 4, 5-bisphosphate (PIP2) at the inner leaflet of the plasma membrane has been proposed to locally regulate the actin cytoskeleton. Indeed, recent studies that use GFP-tagged pleckstrin homology domains (GFP-PH) as fluorescent PIP2sensors suggest that this lipid is enriched in membrane microdomains. Here we report that this concept needs revision. Using three distinct fluorescent GFP-tagged pleckstrin homology domains, we show that highly mobile GFP-PH patches colocalize perfectly with various lipophilic membrane dyes and, hence, represent increased lipid content rather than PIP2-enriched microdomains. We show that bright patches are caused by submicroscopical folds and ruffles in the membrane that can be directly visualized at ∼15 nm axial resolution with a novel numerically enhanced imaging method. F-actin motility is inhibited significantly by agonist-induced PIP2breakdown, and it resumes as soon as PIP2levels are back to normal. Thus, our data support a role for PIP2in the regulation of cortical actin, but they challenge a model in which spatial differences in PIP2regulation of the cytoskeleton exist at a micrometer scale.

Bibliography

van Rheenen, J., & Jalink, K. (2002). Agonist-induced PIP2Hydrolysis Inhibits Cortical Actin Dynamics: Regulation at a Global but not at a Micrometer Scale. Molecular Biology of the Cell, 13(9), 3257â3267.

Authors 2

Jacco van Rheenen (first)
Kees Jalink (additional)

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Dates

Type	When
Created	22 years, 11 months ago (Sept. 10, 2002, 10:16 p.m.)
Deposited	4 years, 3 months ago (May 27, 2021, 5:18 p.m.)
Indexed	2 weeks, 3 days ago (Aug. 19, 2025, 6:47 a.m.)
Issued	23 years ago (Sept. 1, 2002)
Published	23 years ago (Sept. 1, 2002)
Published Print	23 years ago (Sept. 1, 2002)

Funders 0

None

BibTeX

@article{van_Rheenen_2002, title={Agonist-induced PIP2Hydrolysis Inhibits Cortical Actin Dynamics: Regulation at a Global but not at a Micrometer Scale}, volume={13}, ISSN={1939-4586}, url={http://dx.doi.org/10.1091/mbc.e02-04-0231}, DOI={10.1091/mbc.e02-04-0231}, number={9}, journal={Molecular Biology of the Cell}, publisher={American Society for Cell Biology (ASCB)}, author={van Rheenen, Jacco and Jalink, Kees}, editor={Pollard, Thomas D.}, year={2002}, month=sep, pages={3257–3267} }

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  "abstract": "<jats:p>Phosphatidylinositol 4, 5-bisphosphate (PIP<jats:sub>2</jats:sub>) at the inner leaflet of the plasma membrane has been proposed to locally regulate the actin cytoskeleton. Indeed, recent studies that use GFP-tagged pleckstrin homology domains (GFP-PH) as fluorescent PIP<jats:sub>2</jats:sub>sensors suggest that this lipid is enriched in membrane microdomains. Here we report that this concept needs revision. Using three distinct fluorescent GFP-tagged pleckstrin homology domains, we show that highly mobile GFP-PH patches colocalize perfectly with various lipophilic membrane dyes and, hence, represent increased lipid content rather than PIP<jats:sub>2</jats:sub>-enriched microdomains. We show that bright patches are caused by submicroscopical folds and ruffles in the membrane that can be directly visualized at \u223c15 nm axial resolution with a novel numerically enhanced imaging method. F-actin motility is inhibited significantly by agonist-induced PIP<jats:sub>2</jats:sub>breakdown, and it resumes as soon as PIP<jats:sub>2</jats:sub>levels are back to normal. Thus, our data support a role for PIP<jats:sub>2</jats:sub>in the regulation of cortical actin, but they challenge a model in which spatial differences in PIP<jats:sub>2</jats:sub>regulation of the cytoskeleton exist at a micrometer scale.</jats:p>",
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