ArticleCellular signalling2011
The mechanism of cell membrane ruffling relies on a phospholipase D2 (PLD2), Grb2 and Rac2 association.
Article in Cellular signalling, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 44 citations in OpenAlex.
- Encapsulin protein MAV2054 enhances Mycobacterium avium virulence by promoting Cdc42-dependent epithelial cell invasion.Journal of microbiology (Seoul, Korea) · 2025Article
- Engineered In Vitro Platforms for Mechanochemical Control of Cell Migration.Cold Spring Harbor perspectives in biology · 2025Review
- Membrane Ruffles: Composition, Function, Formation and Visualization.International journal of molecular sciences · 2024Review
- Spatiotemporal Coordination of Rac1 and Cdc42 at the Whole Cell Level during Cell Ruffling.Cells · 2023Article
- Review
- The gastrointestinal microbiota in colorectal cancer cell migration and invasion.Clinical & experimental metastasis · 2021Review
- Role of RhoC in cancer cell migration.Cancer cell international · 2021Review
- Visualizing Membrane Ruffle Formation using Scanning Electron Microscopy.Journal of visualized experiments : JoVE · 2021Article
- Structure and regulation of human phospholipase D.Advances in biological regulation · 2021Review
- Improving Receptor-Mediated Intracellular Access and Accumulation of Antibody Therapeutics-The Tale of HER2.Antibodies (Basel, Switzerland) · 2020Review
- Mammalian phospholipase D: Function, and therapeutics.Progress in lipid research · 2020Review
- Tissue specific human fibroblast differential expression based on RNAsequencing analysis.BMC genomics · 2019Article
- Wave patterns organize cellular protrusions and control cortical dynamics.Molecular systems biology · 2019Article
- GRAMD1B regulates cell migration in breast cancer cells through JAK/STAT and Akt signaling.Scientific reports · 2018Article
- Oxidized LDL phagocytosis during foam cell formation in atherosclerotic plaques relies on a PLD2-CD36 functional interdependence.Journal of leukocyte biology · 2018Article
- Systems Analysis of the Liver Transcriptome in Adult Male Zebrafish Exposed to the Plasticizer (2-Ethylhexyl) Phthalate (DEHP).Scientific reports · 2018Article
- Epidermal growth factor receptors containing a single tyrosine in their C-terminal tail bind different effector molecules and are signaling-competent.The Journal of biological chemistry · 2017Article
- Intracellular targeting of annexin A2 inhibits tumor cell adhesion, migration, and in vivo grafting.Scientific reports · 2017Article
- The cell surface environment for pathogen recognition and entry.Clinical & translational immunology · 2016Review
- Chloride channel-3 promotes tumor metastasis by regulating membrane ruffling and is associated with poor survival.Oncotarget · 2015Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Membrane ruffling is the formation of actin rich membrane protrusions, essential for cell motility. The exact mechanism of ruffling is not fully known. Using YFP and CFP fluorescent chimeras, we show for the first time a co-localization of Phospholipase D2 (PLD2) and Growth factor Receptor Bound protein-2 (Grb2) with actin-rich membrane protrusions of macrophages. Grb2 cooperates with PLD2 in enhancing membrane ruffling, whether in resting cells or in cells stimulated with the growth factor M-CSF, although in the latter an increase in dorsal ruffles was observed, consistent with receptor-ligand internalization. Cells transfected with PLD2 mutated in the PH domain (Y169F) or with Grb2 mutated in the SH2 site (R86K) negate this effect, indicating an association PLD2(Y169)-SH2-Grb2 that was confirmed by immunoprecipitation and Western blotting. The association results in enhanced PLD activity, but the lipase activity can only partially explain the formation of membrane ruffles in vivo. A third component involves the Rho-GTPase Rac2 and it is only when Rac2 is overexpressed along with PLD2 and Rac2 that a full biological effect, including actin polymerization in vivo, is obtained. The mechanism involved is, then, as follows: PLD enzymatic action, after having been increased due to the binding to Grb2-SH2 via Y169, cooperates with Rac2, and the three molecules stimulate actin polymerization and consequently, membrane ruffle formation. Since membrane ruffling precedes cell migration, the results herein provide a novel mechanism for control of membrane dynamics, crucial for the physiology of leukocytes.
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