Putative role of the H+/sucrose symporter SLC45A3 as an osmolyte transporter in the kidney

Abstract

The solute carrier family 45 a3 member (SLC45A3), known also as prostein, has been implicated with prostate cancer and the regulation of lipid metabolism in oligodendrocytes. Recently, we expressed SLC45A3 in yeast cells and characterised it as a proton-coupled sucrose symporter. However, the physiological functions of SLC45A3 were still unknown. Here, we report that SLC45A3 occurs in the kidney and is highly expressed in the medullary collecting duct (IMCD), a part of the kidney responsible for final urine concentration and faced to hyperosmotic environment. Moreover, messenger RNA (mRNA) expression of endogenous SLC45A3 in rat IMCD cells as well as in NRK52E cells increased up to four-fold under hyperosmotic conditions at 600 mOsmol/kg. Using NRK52E cells as an experimental model, we investigated the proton-coupled sugar transport and found that the uptake of sucrose or glucose was enhanced by hyperosmolarity. Down-regulation of expression by small interfering RNA (siRNA) decreased the osmotically inducible part of sucrose uptake and confirmed the involvement of SLC45A3 in this process. Furthermore, we observed an up to four-fold elevation of sucrose uptake triggered by hyperosmolarity across the apical membrane of NRK52E cells, while uptake across the basolateral membrane was not affected. Due to this finding, we conclude that SLC45A3 may occur at the luminal side of kidney epithelial cells and thus may take up solutes from the tubular fluid. Altogether, we show that SLC45A3 is a novel sugar transporter in kidney and hypothesise that the disaccharide sucrose, and probably the monosaccharides glucose and fructose, may serve as compatible osmolytes in urine.

Somatostatin receptor subtype 1 as a potential diagnostic marker and therapeutic target in prostate cancer

“…61 This might be an important observation since other growth factors, such as GHRH 62 or gastrin-releasing peptide, 63 have also been described as PCa enhancer, being even used as therapeutic targets. 64 Additionally, SLC45A3 has been shown to be usually present in malignant prostate tissue 65 and LIFR has been previously reported as an unfavorable prognosis marker in melanoma, and to be associated with reduced drug response in breast cancer. 66,67 Therefore, the downregulation of these genes highlights the anti-tumoral function of sst1.…”

The Lymphatic System: Integral Roles in Immunity

“…Some of these selected genes have already been connected to lymphatic valve formation and maintenance (Table 2), yet lymphatic valves have not been described in lymph nodes. Other genes suggest connections that might link lymph node lymphatics to osmolyte transport (135, 136) and pacemaker activity (137). Clearly, there are many new functional connections to be made as we explore lymphatic diversity in full.…”

Putative role of an SLC45 H+/sugar cotransporter in mammalian spermatozoa

“…At pH 6.0, sucrose uptake in the presence of Na + was similar to that in the presence of Li + ( p = 0.11), while elevation of pH from 6.0 to 7.5 led to significant decrease in transport rate ( p = 3.1E–8). The fact that sucrose uptake was not completely deleted in the presence of CCCP is not unexpected because the sucrose gradient itself provides a part of the driving force for transport [ 4 , 33 ].

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“…SLC45 member A1 has been shown to be involved in the uptake of glucose into brain cells during hypercapnia [ 26 ], while SLC45A2 seems to play a significant role in melanin synthesis [ 14 , 20 , 29 ]. SLC45A3 has recently been shown by us to occur in the kidney medulla where it may transport sucrose as a compatible osmolyte from the urine into collecting duct cells [ 33 ]. Furthermore, SLC45A3 was also found in oligodendrocytes where it seems to be involved in myelin maintenance [ 27 ].…”