PUB - Publikationen an der Universität Bielefeld

The transmembrane protein SLC22A17 (or neutrophil gelatinase-associated lipocalin (NGAL)/lipocalin-2 (LCN2)/24p3 receptor) is an atypical member of the SLC22 family of organic anion and cation transporters: It does not carry typical substrates of SLC22 transporters, but mediates receptor-mediated endocytosis (RME) of LCN2. One important task of the kidney is prevention of urinary loss of proteins filtered by the glomerulus by bulk reabsorption of multiple ligands via megalin:cubilin:amnionless-mediated RME in the proximal tubule (PT). Accordingly, overflow, glomerular or PT damage, as in Fanconi syndrome, result in proteinuria. Strikingly, up to 20% of filtered proteins escape the PT under physiological conditions and are reabsorbed by the distal nephron. The kidney distal tubule and collecting duct express SLC22A17, which mediates RME of filtered proteins that evade the PT, but with limited capacity to prevent proteinuria under pathological conditions. The kidney also prevents excretion of filtered essential and non-essential transition metals (TMs), such as iron (Fe) or cadmium (Cd), respectively, that are largely bound to proteins with high, e.g. lipocalin-2 (LCN2), transferrin, or metallothionein, or low affinity, e.g. microglobulins or albumin. Hence, increased uptake of TMs may cause nephrotoxicity. Here we assess the literature on SLC22A17 structure, topology, tissue distribution, regulation and assumed functions, emphasizing renal SLC22A17, which has relevance for physiology, pathology, and nephrotoxicity due to accumulation of proteins complexed with TMs, e.g. Cd or Fe. Other putative renal functions of SLC22A17, such as its contribution to osmotic stress adaptation, protection against urinary tract infection, or renal carcinogenesis, are discussed.