SLC15A4 Membrane Protein Introduction

Introduction of SLC15A4

SLC15A4 is also known as Solute carrier family 15 member 4, Peptide transporter 4, Peptide/histidine transporter 1, and hPHT1. It belongs to the proton-coupled oligopeptide transporters (POTs), which utilizes a proton gradient as the motive force for uphill transport of di/tripeptides and peptide-like compounds across membranes. It is one of the four subtypes of mammalian members, namely PEPT1, PEPT2, PHT1 and PHT2. SLC15A4 contains 12 transmembrane domains with N- and C-termini in the cytosol.

Function of SLC15A4 Membrane Protein

SLC15A4 is significantly expressed in the brain and lymphatic system, and currently is considered endosomal and lysosomal transporters with limited substrate specificity for histidine and certain oligopeptides. Several studies have suggested that SLC15A4 is associated with diabetes, inflammatory bowel disease and systemic lupus erythematosus. Researchers have also reported that SLC15A4 plays a role in NOD and TLR ligands-triggered immune responses. For example, using genetically modified mice, cytokine production mediated by the NOD1 ligand Tri-DAP, was reduced in SLC15A4 deficient mice. Moreover, knockdown of PHT1 significantly decreased Tri-DAP induced NF-κB activation in HEK293T cells. The proton-coupled oligopeptide transporter SLC15A4, which facilitates cross-membrane transport of histidine and small peptides from inside the endosomes or lysosomes to cytosol, plays an important role in intracellular peptide homeostasis and innate immune response. SLC15A4 may serve as a potential target for reducing the immune response and for drug treatment of inflammatory diseases.

Fig.1 Model for the role of SLC15A4 in immune responses (Song, 2018).

Application of SLC15A4 Membrane Protein in Literature

1. Song F., et al. Functional Characterization of Human Peptide/Histidine Transporter 1 in Stably Transfected MDCK Cells. Mol. Pharm. 2018, 15(2):385-393. PubMed ID: 29224352
   
   

   The findings of this article suggest that hPHT1 (SLC15A4) may serve as a potential target for reducing the immune response and for drug treatment of inflammatory diseases.

2. Bhardwaj R.K., et al. The functional evaluation of human peptide/histidine transporter 1 (hPHT1) in transiently transfected COS-7 cells. Eur. J. Pharm. Sci. 2006, 27(5):533-542. PubMed ID: 16289537
   
   

   This article presents the initial functional characterization and protein expression of hPHT1 (SLC15A4). The results of this article suggest that hPHT1 (SLC15A4) could potentially have a significant effect on our current perception of active peptide and peptide-based drug transport.

3. Lindley D.J., et al. The evaluation of peptide/histidine transporter 1 (PHT1) function: uptake kinetics utilizing a cos-7 stably transfected cell line. Revista mexicana de ciencias farmaceutica. 2011, 42(4):57-65. PubMed ID: 23888104
   
   

   This article reveals that stably transfected hPHT1-COS-7 cells exhibit different uptake kinetics than those observed in our previous studies and illustrate the requirement for experiments to delineate the physiological role of hPHT1 (SLC15A4).

4. Zwarycz B., et al. Expression of the peptide transporters PepT1, PepT2, and PHT1 in the embryonic and posthatch chick. Poultry Science. 2013, 92(5):1314-1321. PubMed ID: 23571341
   
   

   The article analyzes the expression pattern of PHT1 (SLC15A4) in all tissues and suggests that expression of PHT1 increased in the jejunum, large intestine, brain, and liver post-hatch and decreased in the proventriculus from embryonic stages to post-hatch.

5. Kobayashi T., et al. Lysosome biogenesis regulated by the amino-acid transporter SLC15A4 is critical for functional integrity of mast cells. Int. Immunol. 2017, 29(12):551-566. PubMed ID: 29155995
   
   

   This article reveals a close relationship between SLC15A4 and secretory-granule biogenesis that is critical for the functional integrity of mast cells. The results of this article demonstrated that SLC15A4 is required for mast-cell secretory-granule homeostasis, and limits mast-cell functions and inflammatory responses by controlling the mTORC1–TFEB signaling axis.

SLC15A4 Preparation Options

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Reference

1. Song F., et al. (2018) Functional Characterization of Human Peptide/Histidine Transporter 1 in Stably Transfected MDCK Cells. Mol. Pharm. 15(2):385-393.

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