The transport of glutamine into mammalian cells.
Glutamine has many important functions in mammalian cells, and glutamine transport across cell membranes has accordingly been extensively studied. In the past few years a number of important glutamine transport proteins have been sequenced and their molecular properties have been characterised. In general, four major transporters are important physiologically. These are known as (i) SNAT3 (System N) which is important in glutamine uptake in periportal cells in liver and in across the basolateral membrane of renal proximal tubule cells and is also involved in glutamine release by liver perivenous cells and by astrocytes; a variant of this protein catalyses glutamine release from skeletal muscle. (ii) SNAT1 (a specific System A sub-type) which is important in glutamine uptake by neuronal cells (iii) ASCT2 which is essential for glutamine uptake by rapidly growing epithelial cells and tumour cells in culture and (iv) the recently discovered brush border membrane transporter B0 AT1 (SLC6A19). Recent studies considered both the importance of ASCT2 in tumour cell growth and the regulation of ASCT2 expression. In SK-Hep hepatoma cells, knockdown of ASCT2 using antisense mRNA has been shown to cause apoptosis. Expression of the ASCT2 transporter in HepG2 hepatoma cells is stimulated by glutamine by a pathway involving the promoter element AGGTGAATGACTT which binds FXR/RXR dimers.
McGivan
John D
JD
Department of Biochemistry, University of Bristol, School of Medical Sciences, University Walk, Bristol BS8 1TD, United Kingdom. j.mcgivan@bris.ac.uk
Bungard
Claire I
CI
D026962:Amino Acid Transport System ASC / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D001692:Biological Transport; D001921:Brain / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D015533:Transcriptional Activation
D026962:Amino Acid Transport System ASC; D002352:Carrier Proteins; D015778:Minor Histocompatibility Antigens; C420506:SLC1A5 protein, human; C037853:glutamine transport proteins; D005973:Glutamine