Golgi targeting of the GLUT1 glucose transporter in lactating mouse mammary gland

Lactose, the major carbohydrate of human milk, is synthesized in the Golgi from glucose and UDP-galactose. The lactating mammary gland is unique in it s requirement for the transport of glucose into Golgi. Glucose transporter- 1 (GLUT1) is the only isoform of the glucose transporter family expressed i n mammary gland. In most cells, GLUT1 is localized to the plasma membrane a nd is responsible for basal glucose uptake; in no other cell type is GLUT1 a Golgi resident. To test the hypothesis that GLUT1 is targeted to Golgi du ring lactation, the amount and subcellular distribution of GLUT1 were exami ned in mouse mammary grand at different developmental stages. Methods inclu ding immunohistochemistry, immunofluorescence, subcellular fractionation, d ensity gradient centrifugation, and Western blotting yielded consistent res ults, In virgins, GLUT1 expression was limited to plasma membrane of epithe lial cells. in late pregnant mice, GLUT1 expression was increased with targ eting primarily to basolateral plasma membrane but also with some intracell ular signal. During lactation, GLUT1 expression was further increased, and targeting to Golgi, demonstrated by colocalization with the 110-kD coatomer -associated protein beta-COP, predominated. Removal of pups 18 d after deli very resulted in retargeting of GLUT1 from Golgi to plasma membrane and a d ecline in total cellular GLUT1 within 3 h. In mice undergoing natural weani ng, GLUT1 expression declined. Changes in the amount and targeting of GLUT1 during mammary gland development are consistent with a key role for GLUT1 in supplying substrate for lactose synthesis and milk production.