title: hPepT1 selectively transports muramyl dipeptide but not Nod1-activating muramyl peptides.
abstract: Muramyl peptides derived from bacterial peptidoglycan are detected intracellularly by Nod1 and Nod2, 2 members of the newly characterized nod-like receptor (NLR) family of pattern recognition molecules. In the absence of bacterial invasion into the host cytosolic compartment, it remains unclear whether muramyl peptides can cross the plasma membrane and localize into the cytosol. We have recently demonstrated that the plasma membrane transporter, hPepT1, was able to efficiently translocate muramyl dipeptide (MDP), a specific Nod2-activating molecule, into host cells. We aimed to characterize the transport properties of hPepT1 towards a spectrum of muramyl peptides, including Nod1-activating molecules. To do so, we designed an original procedure based on the ectopic expression of hPepT1 in oocytes from Xenopus laevis. Our results demonstrated that hPepT1 transports MDP but no other Nod2-activating molecule. Moreover, we observed that Nod1-stimulating muramyl peptides were not transported by hPepT1. Since hPepT1 expression is strongly associated with intestinal epithelial cells, where Nod1 and Nod2 have been shown to play a key role, these observations suggest a distinct contribution of Nod1 and Nod2 in mucosal homeostasis following the cellular uptake of muramyl peptides by hPepT1.
authors.affiliation: Laboratory of Molecular Gastroenterology and Hepatology, Department of Internal Medicine, University Hospital Zurich, Switzerland.
authors.forename: Manfred G
authors.initials: MG
authors.lastname: Ismair
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Vavricka
authors.forename: Gerd A
authors.initials: GA
authors.lastname: Kullak-Ublick
authors.forename: Michael
authors.initials: M
authors.lastname: Fried
authors.forename: Dominique
authors.initials: D
authors.lastname: Mengin-Lecreulx
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Girardin
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D004151:Dipeptides / Q000378:metabolism; D006801:Humans; D008845:Microinjections; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism*; D009865:Oocytes; D000074011:Peptide Transporter 1; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D004151:Dipeptides; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D000074011:Peptide Transporter 1; C082186:SLC15A1 protein, human; D027981:Symporters; C004194:glycylsarcosine; D000119:Acetylmuramyl-Alanyl-Isoglutamine