hPepT1 selectively transports muramyl dipeptide but not Nod1-activating muramyl peptides

Manfred G Ismair1, Stephan R Vavricka, Gerd A Kullak-Ublick

  • 1Laboratory of Molecular Gastroenterology and Hepatology, Department of Internal Medicine, University Hospital Zurich, Switzerland.

Insights

The human peptide transporter 1 (hPepT1) imports muramyl dipeptide (MDP) into cells, but not other Nod1 or Nod2 activating muramyl peptides. This suggests distinct roles for Nod1 and Nod2 in gut immunity.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Muramyl peptides from bacteria are recognized by intracellular pattern recognition receptors Nod1 and Nod2.
  • The mechanism by which these peptides cross the plasma membrane into the cytosol is unclear.
  • The peptide transporter hPepT1 was previously shown to transport muramyl dipeptide (MDP).

Purpose of the Study:

  • To investigate the transport capabilities of hPepT1 for various muramyl peptides.
  • To determine if hPepT1 transports Nod1-activating muramyl peptides.
  • To understand the cellular uptake of muramyl peptides in the context of innate immunity.

Main Methods:

  • Ectopic expression of hPepT1 in Xenopus laevis oocytes.
  • Characterization of hPepT1 transport activity using a range of muramyl peptides.
  • Analysis of transport specificity for Nod1 and Nod2 agonists.

Main Results:

  • hPepT1 efficiently transported muramyl dipeptide (MDP), a Nod2 agonist.
  • hPepT1 did not transport other tested Nod2-activating muramyl peptides.
  • Nod1-stimulating muramyl peptides were not substrates for hPepT1.
  • hPepT1 expression is prominent in intestinal epithelial cells.

Conclusions:

  • hPepT1 exhibits specific transport for MDP, influencing Nod2 activation.
  • The lack of transport for other muramyl peptides suggests differential cellular entry pathways.
  • Distinct roles for Nod1 and Nod2 in mucosal homeostasis may arise from specific peptide uptake mechanisms mediated by hPepT1.

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