PHOSPHATIDYLCHOLINE TRANSLOCASE - A PHYSIOLOGICAL-ROLE FOR THE MDR2 GENE

被引:547
作者
RUETZ, S
GROS, P
机构
[1] Department of Biochemistry McGill University Montreal
基金
英国医学研究理事会;
关键词
D O I
10.1016/0092-8674(94)90446-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
P-glycoproteins (P-gps) encoded by the mouse mdr2 and mdr3 genes were expressed in secretory vesicles (SVs) from the yeast mutant sec6-4, and their capacity to function as a lipid translocase/flippase was tested. An assay that uses a fluorescent phosphatidylcholine (PC) analog was developed to quantitate asymmetric lipid distribution in the outer and inner leaflets of the lipid bilayer of these vesicles. Mdr2 expression in SVs caused a time- and temperature-dependent enhancement of PC translocation to the inner leaflet of the membrane. The Mdr2-mediated effect was specific since expression of Mdr3 in these vesicles was without effect on the membrane distribution of PC. Increased Mdr2-mediated PC translocation was strictly ATP and Mg2+ dependent, was abrogated by the ATPase inhibitor vanadate and the P-gp modulator verapamil, but was insensitive to the presence of excess of the multidrug resistance drugs colchicine and vinblastine.
引用
收藏
页码:1071 / 1081
页数:11
相关论文
共 56 条
[1]   THE MULTIDRUG RESISTANCE (MDR1) GENE-PRODUCT FUNCTIONS AS AN ATP CHANNEL [J].
ABRAHAM, EH ;
PRAT, AG ;
GERWECK, L ;
SENEVERATNE, T ;
ARCECI, RJ ;
KRAMER, R ;
GUIDOTTI, G ;
CANTIELLO, HF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (01) :312-316
[2]   THE GENE ENCODING MULTIDRUG RESISTANCE IS INDUCED AND EXPRESSED AT HIGH-LEVELS DURING PREGNANCY IN THE SECRETORY EPITHELIUM OF THE UTERUS [J].
ARCECI, RJ ;
CROOP, JM ;
HORWITZ, SB ;
HOUSMAN, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (12) :4350-4354
[3]  
BERR F, 1993, J BIOL CHEM, V268, P3976
[4]   ASSEMBLY OF THE ENDOPLASMIC-RETICULUM PHOSPHOLIPID-BILAYER - THE PHOSPHATIDYLCHOLINE TRANSPORTER [J].
BISHOP, WR ;
BELL, RM .
CELL, 1985, 42 (01) :51-60
[5]   HEPATIC TRANSPORT-SYSTEMS REGULATING PHI, CELL-VOLUME, AND BILE SECRETION [J].
BOYER, JL ;
GRAF, J ;
MEIER, PJ .
ANNUAL REVIEW OF PHYSIOLOGY, 1992, 54 :415-438
[6]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[7]  
BRUGGEMANN EP, 1992, J BIOL CHEM, V267, P21020
[8]   FUNCTIONAL-ANALYSIS OF CHIMERIC GENES OBTAINED BY EXCHANGING HOMOLOGOUS DOMAINS OF THE MOUSE MDR1 AND MDR2 GENES [J].
BUSCHMAN, E ;
GROS, P .
MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (02) :595-603
[9]  
BUSCHMAN E, 1992, J BIOL CHEM, V267, P18093
[10]   INTERNAL DUPLICATION AND HOMOLOGY WITH BACTERIAL TRANSPORT PROTEINS IN THE MDR1 (P-GLYCOPROTEIN) GENE FROM MULTIDRUG-RESISTANT HUMAN-CELLS [J].
CHEN, CJ ;
CHIN, JE ;
UEDA, K ;
CLARK, DP ;
PASTAN, I ;
GOTTESMAN, MM ;
RONINSON, IB .
CELL, 1986, 47 (03) :381-389