Sweet taste receptor subunit T1R3 regulates casein secretion and phosphorylation of STAT5 in mammary epithelial cells

During lactation, mammary epithelial cells (MECs) on the apical membrane are in contact with lactose in milk, while MECs on the basolateral membrane are in contact with glucose in blood. Both glucose and lactose are sweeteners that are sensed by a sweet taste receptor. Previously, we have shown that lactose exposure on the basolateral membrane, but not the apical membrane, inhibits casein production and phosphorylation of STAT5 in MECs. However, it remains unclear whether MECs have a sweet taste receptor. In this study, we confirmed that the sweet taste receptor subunit T1R3 existed in both the apical and basolateral membranes of MECs. Subse-quently, we investigated the influence of apical and basolateral sucralose as a ligand for the sweet taste receptor using a cell culture model. In this model, upper and lower media were separated by the MEC layer with less-permeable tight junctions. The results showed in the absence of glucose, both apical and basolateral sucralose induced phosphorylation of STAT5, which is a positive transcriptional factor for milk production. In contrast, the T1R3 inhibitor basolateral lactisole reducing phosphorylated STAT5 and secreted caseins in the presence of glucose. Furthermore, exposure of the apical membrane to sucralose in the presence of glucose inhibited the phosphorylation of STAT5. Simultaneously, GLUT1 was partially translocated from the basolateral membrane to the cytoplasm in MECs. These results suggest that T1R3 functions as a sweet receptor and is closely involved in casein production in MECs.

Automated summary

A sweet taste receptor subunit T1R3 was found in both the apical and basolateral membranes of mammary epithelial cells (MECs). In a cell culture model, sucralose on both the apical and basolateral membranes activated the sweet taste receptor, leading to increased phosphorylation of STAT5, which is involved in milk production.