Second International Ringberg Conference: ?Cell Biology and Molecular Basis of Liver Transport?

Abstract

In the 7 years since the 1st Ringberg conference on ''He-observed system is a Cif-transporter, which means that it is patic Transport of Organic Substances'' was held at Ringberg-specific for purines and uridine. The transporter was cloned Castle near Tegernsee in Bavaria, Germany, the molecular very recently by expression cloning in Xenopus laevis oobasis of transport in the liver has been investigated with cytes. 2 The 2.9-kb complementary DNA of the Na / -dependent great success. Several carrier proteins could be cloned and purine nucleoside transporter SPNT encodes a protein of 659 the molecular properties of hepatic transport systems are amino acid residues and an estimated molecular mass of 72 now better understood, e.g., their function, architecture, kd. Hydropathy analysis reveals 14 putative membrane spanmembrane insertion, expression, and subcellular localization. ning segments. In addition, new insights into the cell biology of hepatocelluMdr transporters, synonym P-glycoproteins, were discovlar membrane transport were obtained, including transport ered as plasma membrane transport ATPases that are overregulation by signal-transduction cascades and the involve-expressed in multidrug-resistant tumor cells. Mdr2 is a phosment of transport systems in pH homeostasis and cell volume pholipid translocator, whereas mdr1 and mdr3 confer the regulation. These items were the topics of the 2nd Interna-transport of drugs into bile. S. Ruetz (Montréal, Quebec, Cantional Ringberg Conference on ''Cell Biology and Molecular ada) presented results regarding the detailed characterizaBasis of Liver Transport.'' tion of mdr2-mediated phosphatidylcholine (PC) translocation in the canalicular membrane. Yeast mutants of the sec BIOCHEMISTRY AND MOLECULAR BIOLOGY6-4 strain, which expressed the mdr2 protein in the mem- OF TRANSPORTbrane of yeast secretory vesicles, were generated. By use of the fluorescent PC label 7-nitrobenzoxa-1,3-diazol phosphatiThe recent discovery of canalicular primary active trans-dylcholine, he finds that the mdr2 protein translocates specifport systems that are involved in the vectorial transport of ically PC but not phosphatidylethanolamine or phosphatidylcholephilic compounds into bile has markedly stimulated the serine from the outer leaflet to the inner leaflet of the vesicles. understanding of bile formation. Previous to this era, the This translocation is affected by vanadate and verapamil, but adenosine triphosphatase (ATPase) activity of canalicular it is insensitive to vesicle acidification or membrane depolarmembranes was mainly attributed to a Ca 2/ Mg 2/ -ATPase, ization. 3 When the vesicles accumulate taurocholate, PC an ectoenzyme cloned in 1989 by Lin and Guidotti. 1 As re-translocation is stimulated. Fifty micromoles of the bile acid viewed by I. M. Arias (Boston, MA), these enzymes degrade can act as a potential lipid solubilizer, extracting 7-nitroextracellular (intraluminal) adenosine triphosphate (ATP) to benzoxa-1,3-diazol phosphatidylcholine molecules from the adenosine diphosp...

Infection of Polarized Cultures of Human Intestinal Epithelial Cells with Hepatitis A Virus: Vectorial Release of Progeny Virions through Apical Cellular Membranes

“…Thus, it is likely that apical secretion of HAV from hepatocytes occurs by a process that is different from apical secretion in infected Caco-2 cells. Nonetheless, some canalicular (apical) glycophosphatidylinositol-linked proteins may reach their final destination by a direct transport mechanism in hepatocytes (38). In addition, cellular transport proteins have been identified which function in the direct transport of biliary lipids and bile salts to the canalicular surface (6).…”

Uptake of Taurocholic Acid in Human Hepatocytes Isolated From Livers of Donors of Different Age

“…Interestingly, Suchy and Balistreri (1) reported that in rat hepatocytes from developing rats (until puberty), no difference in affinity for the carrier was observed during maturation, but that the number of binding sites or transport sites was reduced compared with the number in mature rats. Moreover, posttranslational protein modification of the carrier may still be insufficient in developing rats (10).…”