Phosphatidylethanolamine critically supports internalization of cell-penetrating protein C inhibitor.

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License: CC BY-NC-SA 4.0
Serval ID
serval:BIB_5F1E18D3CB68
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Phosphatidylethanolamine critically supports internalization of cell-penetrating protein C inhibitor.
Journal
Journal of Cell Biology
Author(s)
Baumgärtner P., Geiger M., Zieseniss S., Malleier J., Huntington J.A., Hochrainer K., Bielek E., Stoeckelhuber M., Lauber K., Scherfeld D., Schwille P., Wäldele K., Beyer K., Engelmann B.
ISSN
1540-8140 (Electronic)
ISSN-L
0021-9525
Publication state
Published
Issued date
2007
Volume
179
Number
4
Pages
793-804
Language
english
Abstract
Although their contribution remains unclear, lipids may facilitate noncanonical routes of protein internalization into cells such as those used by cell-penetrating proteins. We show that protein C inhibitor (PCI), a serine protease inhibitor (serpin), rapidly transverses the plasma membrane, which persists at low temperatures and enables its nuclear targeting in vitro and in vivo. Cell membrane translocation of PCI necessarily requires phosphatidylethanolamine (PE). In parallel, PCI acts as a lipid transferase for PE. The internalized serpin promotes phagocytosis of bacteria, thus suggesting a function in host defense. Membrane insertion of PCI depends on the conical shape of PE and is associated with the formation of restricted aqueous compartments within the membrane. Gain- and loss-of-function mutations indicate that the transmembrane passage of PCI requires a branched cavity between its helices H and D, which, according to docking studies, precisely accommodates PE. Our findings show that its specific shape enables cell surface PE to drive plasma membrane translocation of cell-penetrating PCI.
Keywords
Animals, Binding Sites, Biotin/metabolism, Blood Platelets/chemistry, Blood Platelets/metabolism, Cell Membrane/chemistry, Cell Membrane/metabolism, Cell Nucleus/metabolism, Fluorescent Antibody Technique, Indirect, Granulocytes/metabolism, HL-60 Cells, Humans, Iodine Radioisotopes/metabolism, Leukocytes/pathology, Leukocytes/ultrastructure, Mice, Mutation, Phosphatidylethanolamines/metabolism, Platelet Activation/drug effects, Protein Binding, Protein C Inhibitor/chemistry, Protein C Inhibitor/genetics, Recombinant Proteins/metabolism, Thrombin/pharmacology, Time Factors
Pubmed
Web of science
Open Access
Yes
Create date
24/05/2013 16:58
Last modification date
02/04/2020 6:19
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