Syndecan-1 and syndecan-4 can mediate the invasion of OpaHSPG-expressing Neisseria gonorrhoeae into epithelial cells.
Neisseria gonorrhoeae (Ngo) expressing the outer membrane protein OpaHSPG can adhere to and invade epithelial cells via binding to heparan sulphate proteoglycan (HSPG) receptors. In this study, we have investigated the role of syndecan-1 and syndecan-4, two members of the HSPG family, in the uptake of Ngo by epithelial cells. When overexpressed in HeLa cells, both syndecans co-localize with adherent Ngo on the host cell surface. This overexpression of syndecan-1 and syndecan-4 leads to a three- and sevenfold increase in Ngo invasion respectively. In contrast, transfection with the syndecan-1 and syndecan-4 mutant constructs lacking the intracellular domain results in an abrogation of the invasion process, characteristic of a dominant-negative mode of action. A concomitant loss of the capacity to mediate Ngo uptake was also observed with syndecan-4 mutant constructs carrying lesions in the dimerization motif necessary for the binding of protein kinase C (PKC) and phosphatidylinositol 4,5-bisphosphate (PIP2), and mutants that are deficient in a C-terminal EFYA amino acid motif responsible for binding to syntenin or CASK. We conclude that syndecan-1 and syndecan-4 can both mediate Ngo uptake into epithelial cells, and that their intracellular domains play a crucial role in this process, perhaps by mediating signal transduction or anchorage to the cytoskeleton.
Freissler
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E
Max-Planck-Institut für Biologie, Abteilung Infektionsbiologie, Tübingen, Germany.
Meyer auf der Heyde
A
A
David
G
G
Meyer
T F
TF
Dehio
C
C
D000595:Amino Acid Sequence; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology*; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D009344:Neisseria gonorrhoeae / Q000472:pathogenicity*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017384:Sequence Deletion; D053668:Syndecan-1; D053671:Syndecan-4; D053667:Syndecans; D014162:Transfection; D014407:Tumor Cells, Cultured
D001425:Bacterial Outer Membrane Proteins; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508241:SDC1 protein, human; C508304:SDC4 protein, human; D053668:Syndecan-1; D053671:Syndecan-4; D053667:Syndecans; D011493:Protein Kinase C