Version 1
: Received: 15 December 2023 / Approved: 18 December 2023 / Online: 18 December 2023 (13:29:59 CET)
How to cite:
Pujol-Giménez, J.; Hediger, M.A. Functional Characterization of the Lysosomal Peptide/Histidine Transporter PHT1 (SLC15A4) by Solid Supported Membrane Electrophysiology (SSME). Preprints2023, 2023121302. https://doi.org/10.20944/preprints202312.1302.v1
Pujol-Giménez, J.; Hediger, M.A. Functional Characterization of the Lysosomal Peptide/Histidine Transporter PHT1 (SLC15A4) by Solid Supported Membrane Electrophysiology (SSME). Preprints 2023, 2023121302. https://doi.org/10.20944/preprints202312.1302.v1
Pujol-Giménez, J.; Hediger, M.A. Functional Characterization of the Lysosomal Peptide/Histidine Transporter PHT1 (SLC15A4) by Solid Supported Membrane Electrophysiology (SSME). Preprints2023, 2023121302. https://doi.org/10.20944/preprints202312.1302.v1
APA Style
Pujol-Giménez, J., & Hediger, M.A. (2023). Functional Characterization of the Lysosomal Peptide/Histidine Transporter PHT1 (SLC15A4) by Solid Supported Membrane Electrophysiology (SSME). Preprints. https://doi.org/10.20944/preprints202312.1302.v1
Chicago/Turabian Style
Pujol-Giménez, J. and Matthias A Hediger. 2023 "Functional Characterization of the Lysosomal Peptide/Histidine Transporter PHT1 (SLC15A4) by Solid Supported Membrane Electrophysiology (SSME)" Preprints. https://doi.org/10.20944/preprints202312.1302.v1
Abstract
Peptide/Histidine Transporter PHT1 (SLC15A4) is expressed in lysosomal membranes of immune cells where it plays an important role in metabolic and inflammatory signaling. PHT1 is an H+-coupled/histidine symporter that can transport a broad range of oligopeptides, including a variety of bacterial-derived peptides. Moreover, it enables the scaffolding of various metabolic signaling molecules and interacts with key regulatory elements of the immune response. Therefore, it is not surprising that PHT1 is associated with the development of autoimmune diseases, such as systemic lupus erythematosus (SLE). Unfortunately, the pharmacological development of PHT1 has been hampered by the lack of appropriate transport assays. With the aim to address this shortcoming, a novel transport assay based on solid supported membrane-based electrophysiology (SSME) is presented. Key findings of the present SSME studies include the first recordings of electrophysiological properties, a pH dependence analysis, an assessment of PHT1 substrate selectivity, as well as the transport kinetics of the identified substrates. In contrast to previous works, PHT1 is studied its native lysosomal environment. Moreover, observed substrate selectivity is validated by molecular docking. Overall, this new SSME-based assay is expected to contribute to unlock the pharmacological potential of PHT1 and to deepen the understanding of its functional properties.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
