0000000000123200
AUTHOR
Sabine Brast
DS_DISC859837 – Supplemental material for Identification of the Tetraspanin CD9 as an Interaction Partner of Organic Cation Transporters 1 and 2
Supplemental material, DS_DISC859837 for Identification of the Tetraspanin CD9 as an Interaction Partner of Organic Cation Transporters 1 and 2 by Beatrice Snieder, Sabine Brast, Alexander Grabner, Sven Buchholz, Rita Schröter, Gilles A. Spoden, Luise Florin, Johanna Salomon, Tobias Albrecht, Vivien Barz, Alex Sparreboom and Giuliano Ciarimboli in SLAS Discovery
Tetraspanin CD63 controls basolateral sorting of organic cation transporter 2 in renal proximal tubules.
CD63 is a ubiquitously expressed member of the tetraspanin superfamily. Using a mating-based split-ubiquitin-yeast 2-hybrid system, pull-down experiments, total internal reflection fluorescence microscopy, Forster resonance energy transfer, and biotinylation assays, we found that CD63 interacts with human organic cation transporter 2 (hOCT2), which transports endogenous and exogenous substrates, such as neurotransmitters and drugs in several epithelial cells. CD63 overexpression affects cellular localization of hOCT2 expressed in human embryonic kidney (HEK)293 cells. Studies with CD63-knockout mice indicate that in renal proximal tubules, CD63 determines the insertion of the mouse ortholog…
Identification of the Tetraspanin CD9 as an Interaction Partner of Organic Cation Transporters 1 and 2
Organic cation transporters (OCTs) are membrane proteins with relevant physiological (because they accept neurotransmitters as substrate) and pharmacological (because of their interaction with drugs) roles. The human OCTs hOCT1 (SLC22A1/hOCT1) and hOCT2 (SLC22A2/hOCT2) are highly expressed in hepatic (hOCT1) and in renal and neuronal tissue (hOCT2), suggesting a possible role in modulating neurotransmitter activity in the liver, kidney, and brain, and their clearance from the blood. Even though there are several data demonstrating that OCTs are regulated under various patho-physiological conditions, it remains largely unknown which proteins directly interact with OCTs and thereby influence …