Expression of a Non-MDR2-Coded Liver Phosphatidylcholine Membrane Transport Protein inXenopus laevisOocytes

Cornacchia, Luigi; Domdey, Horst; Mössner, Joachim; Berr, Frieder

doi:10.1006/bbrc.1997.6081

Cited by 2 publications

(3 citation statements)

References 29 publications

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“…In addition, a PC translocator has been identified in canalicular membranes of rat liver, that exhibits kinetic properties similar to those of a PC translocator in the ER that was characterized previously [54]. This latter translocator is unrelated to the mdr2 protein [55], which, as will be discussed below, also acts as a translocator of PC in bile canalicular membranes [56,57]. Finally, the MDR1 P-glycoprotein and the MDR-related protein MRP1 were shown to display lipidtranslocating properties [58].…”

Section: Cell-surface Transport Of Lipids Lipid Diversity In Cellularmentioning

confidence: 62%

“…Indeed, in itro studies in which the mdr2 protein was expressed in a yeast secretion mutant revealed an ATP-dependent PC translocase activity of the mdr2 protein [57]. In addition to mdr2, another, structurally unrelated ATPindependent PC translocator has been demonstrated in canalicular membranes [54,55].…”

Section: The Role Of Mdr2 In Biliary Lipid Transport and Its Implicatmentioning

confidence: 99%

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Mechanisms and functional features of polarized membrane traffic in epithelial and hepatic cells

Zegers

Hoekstra

1998

Biochemical Journal

135

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Epithelial cells express plasma-membrane polarity in order to meet functional requirements that are imposed by their interaction with different extracellular environments. Thus apical and basolateral membrane domains are distinguished that are separated by tight junctions in order to maintain the specific lipid and protein composition of each domain. In hepatic cells, the plasma membrane is also polarized, containing a sinusoidal (basolateral) and a bile canalicular (apical)-membrane domain. Relevant to the biogenesis of these domains are issues concerning sorting, (co-)transport and regulation of transport of domain-specific membrane components. In epithelial cells, specific proteins and lipids, destined for the apical membrane, are sorted in the trans-Golgi network (TGN), which involves their sequestration into cholesterol/sphingolipid 'rafts', followed by 'direct' transport to the apical membrane. In hepatic cells, a direct apical transport pathway also exists, as revealed by transport of sphingolipids from TGN to the apical membrane. This is remarkable, since in these cells numerous apical membrane proteins are 'indirectly' sorted, i.e. they are first transferred to the basolateral membrane prior to their subsequent transcytosis to the apical membrane. This raises intriguing questions as to the existence of specific lipid rafts in hepatocytes. As demonstrated in studies with HepG2 cells, it has become evident that, in hepatic cells, apical transport pathways can be regulated by protein kinase activity, which in turn modulates cell polarity. Finally, an important physiological function of hepatic cells is their involvement in intracellular transport and secretion of bile-specific lipids. Mechanisms of these transport processes, including the role of multidrug-resistant proteins in lipid translocation, will be discussed in the context of intracellular vesicular transport. Taken together, hepatic cell systems provide an important asset to studies aimed at elucidating mechanisms of sorting and trafficking of lipids (and proteins) in polarized cells in general.

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Section: Cell-surface Transport Of Lipids Lipid Diversity In Cellularmentioning

confidence: 62%

Section: The Role Of Mdr2 In Biliary Lipid Transport and Its Implicatmentioning

confidence: 99%

Mechanisms and functional features of polarized membrane traffic in epithelial and hepatic cells

Zegers

Hoekstra

1998

Biochemical Journal

135

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“…The simplest explanation for this specificity would be if only Pgp translocates these PC subtypes, because otherwise a surplus of phospholipid with long fatty acyl chains would build up in the canalicular membrane, which would require back-flipping of nonextracted phospholipids. Although an ATP-independent flippase function has been described in canalicular membrane fractions, its specificity for nonextracted phospholipids was not investigated (308). The preference for translocation of short-chain PC might be explained by assuming that this PC subtype more easily detaches laterally from the lipid leaflet to enter into the binding cavity of Pgp in the membrane.…”

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confidence: 99%

Mammalian ABC Transporters in Health and Disease

Borst

Elferink

2002

Annu. Rev. Biochem.

1,411

1,152

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f Abstract The ATP-binding cassette (ABC) transporters are a family of large proteins in membranes and are able to transport a variety of compounds through membranes against steep concentration gradients at the cost of ATP hydrolysis. The available outline of the human genome contains 48 ABC genes; 16 of these have a known function and 14 are associated with a defined human disease. Major physiological functions of ABC transporters include the transport of lipids, bile salts, toxic compounds, and peptides for antigen presentation or other purposes. We review the functions of mammalian ABC transporters, emphasizing biochemical mechanisms and genetic defects. Our overview illustrates the importance of ABC transporters in human physiology, toxicology, pharmacology, and disease. We focus on three topics: (a) ABC transporters transporting drugs (xenotoxins) and drug conjugates. (b) Mammalian secretory epithelia using ABC transporters to excrete a large number of substances, sometimes against a steep concentration gradient. Several inborn errors in liver metabolism are due to mutations in one of the genes for these pumps; these are discussed. (c) A rapidly increasing number of ABC transporters are found to play a role in lipid transport. Defects in each of these transporters are involved in human inborn or acquired diseases.

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Expression of a Non-MDR2-Coded Liver Phosphatidylcholine Membrane Transport Protein inXenopus laevisOocytes

Cited by 2 publications

References 29 publications

Mechanisms and functional features of polarized membrane traffic in epithelial and hepatic cells

Mechanisms and functional features of polarized membrane traffic in epithelial and hepatic cells

Mammalian ABC Transporters in Health and Disease

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