ArticleProceedings of the National Academy of Sciences of the United States of America2009
Erythrocyte scaffolding protein p55/MPP1 functions as an essential regulator of neutrophil polarity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Pirinixic Acid Protects Against Hemorrhagic Shock by Regulating Neutrophil-Associated Key Genes.Shock (Augusta, Ga.) · 2026Article
- Effects of Superficial Scratching and Engineered Nanomaterials on Skin Gene Profiles and Microbiota in SKH-1 Mice.International journal of molecular sciences · 2023Article
- Review
- Peripheral Ischemia Imprints Epigenetic Changes in Hematopoietic Stem Cells to Propagate Inflammation and Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Exploring the immune microenvironment of osteosarcoma through T cell exhaustion-associated gene expression: a study on prognosis prediction.Frontiers in immunology · 2023Article
- Gene expression profile associated with Asmt knockout-induced depression-like behaviors and exercise effects in mouse hypothalamus.Bioscience reports · 2022Article
- MPP1 Determines the Mobility of Flotillins and Controls the Confinement of Raft-Associated Molecules.Cells · 2022Article
- Molecular characterization of direct interactions between MPP1 and flotillins.Scientific reports · 2021Article
- Effect of pore size and spacing on neovascularization of a biodegradble shape memory polymer perivascular wrap.Journal of biomedical materials research. Part A · 2021Article
- Not Just Another Scaffolding Protein Family: The Multifaceted MPPs.Molecules (Basel, Switzerland) · 2020Review
- Article
- Protein Palmitoylation in Leukocyte Signaling and Function.Frontiers in cell and developmental biology · 2020Review
- A High-Resolution Map of SBP1 Interactomes in Plasmodium falciparum-infected Erythrocytes.iScience · 2019Article
- Downregulating SynCAM and MPP6 expression is associated with ovarian cancer progression.Oncology letters · 2019Article
- Comparative Analysis of the Transcriptome and Proteome during Mouse Placental Development.Journal of proteome research · 2019Article
- The membrane palmitoylated protein, MPP6, is involved in myelin formation in the mouse peripheral nervous system.Histochemistry and cell biology · 2019Article
- The microdomain-organizing protein MPP1 is required for insulin-stimulated activation of H-Ras.Oncotarget · 2018Article
- Saa3 is a key mediator of the protumorigenic properties of cancer-associated fibroblasts in pancreatic tumors.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- MPP1 as a Factor Regulating Phase Separation in Giant Plasma Membrane-Derived Vesicles.Biophysical journal · 2015Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
As mediators of innate immunity, neutrophils respond to chemoattractants by adopting a highly polarized morphology. Efficient chemotaxis requires the formation of one prominent pseudopod at the cell front characterized by actin polymerization, while local inhibition suppresses the formation of rear and lateral protrusions. This asymmetric control of signaling pathways is required for directional migration along a chemotactic gradient. Here, we identify the MAGUK protein p55/MPP1 as a mediator of the frontness signal required for neutrophil polarization. We developed a p55 knockout (p55(-/-)) mouse model, and demonstrate that p55(-/-) neutrophils form multiple transient pseudopods upon chemotactic stimulation, and do not migrate efficiently in vitro. Upon agonist stimulation, p55 is rapidly recruited to the leading edge of neutrophils in mice and humans. Total F-actin polymerization, along with Rac1 and RhoA activation, appear to be normal in p55(-/-) neutrophils. Importantly, phosphorylation of Akt is significantly decreased in p55(-/-) neutrophils upon chemotactic stimulation. The activity of immunoprecipitated phosphatidylinositol 3-kinase gamma (PI3Kgamma), responsible for chemoattractant-induced synthesis of PIP(3) and Akt phosphorylation, is unperturbed in p55(-/-) neutrophils. Although the total amount of PIP(3) is normal in p55(-/-) neutrophils, PIP(3) is diffusely localized and forms punctate aggregates in activated p55(-/-) neutrophils, as compared to its accumulation at the leading edge membrane in the wild type neutrophils. Together, these results show that p55 is required for neutrophil polarization by regulating Akt phosphorylation through a mechanism that is independent of PI3Kgamma activity.
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Registered trials
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.