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The role of mdr2 P‐glycoprotein in hepatobiliary lipid transport
Author(s) -
Elferink Ronald P. J. Oude,
Tytgat Guido N. J.,
Groen Albert K.
Publication year - 1997
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.11.1.9034162
Subject(s) - secretion , phospholipid , p glycoprotein , transporter , microbiology and biotechnology , atp binding cassette transporter , chemistry , biochemistry , glycoprotein , transport protein , hepatocyte , biology , in vitro , membrane , multiple drug resistance , gene , antibiotics
The small apical (canalicular) domains of hepatocytes form a luminal meshwork of tubules between adjacent hepatocytes and are the sites of primary bile formation. Organic compounds are transported across this membrane domain against high concentration gradients. It has been recognized in recent years that the hepatocyte is harnessed with a set of canalicular ATP‐dependent transport proteins, specialized in this uphill transport. Bile salts, organic anions, cations, and neutral amphipaths are all pumped into the bile via such primary active transporters. Functionally, these transporters resemble ABC transporters overex‐pressed in cells with the multidrug resistance phe‐notype. Indeed, those transporters that have been characterized at the molecular level turn out to be new, or already recognized, members of this family. Phospholipid secretion across the canalicular membrane of the mouse is also mediated by a mem‐ber of this family, mdr2 P‐glycoprotein. This was demonstrated by the absence of phospholipid secre‐tion into bile of mice with a disrupted mdr2 gene and by subsequent demonstration of phospholipid translocation in cells that overexpress this protein. The recognition of mdr2 P‐glycoprotein as a phospholipid flippase sheds new light on the function of P‐glycoproteins and is an important step in understanding the mechanism of biliary lipid secretion.— Oude Elferink, R. P. J., Tytgat, G. N. J., and Groen, A. K. The role of mdr2 P‐glycoprotein in hepatobiliary lipid transport. FASEB J. 11, 19‐28 (1997)