TY  - JOUR
A1  - Mateus Fernández, Sara
A1  - Holló, Zsolt
A1  - Kern, Andras
A1  - Bakos, Éva
A1  - Fischer, Paul A.
A1  - Borst, Piet
A1  - Evers, Raymond
T1  - Role of the N-terminal transmembrane region of the multidrug resistance protein MRP2 in routing to the apical membrane in MDCKII cells
T2  - Journal of biological chemistry
N2  - In polarized cells, the multidrug resistance protein MRP2 is localized in the apical plasma membrane, whereas MRP1, another multidrug resistance protein (MRP) family member, is localized in the basolateral membrane. MRP1 and MRP2 are thought to contain an N-terminal region of five transmembrane segments (TMD0) coupled to 2 times six transmembrane segments via an intracellular loop (L0). We previously demonstrated for MRP1 that a mutant lacking TMD0 but still containing L0, called L0ΔMRP1, was functional and routed to the lateral plasma membrane. To investigate the role of the TMD0L0 region of MRP2 in routing to the apical membrane, we generated mutants similar to those made for MRP1. In contrast to L0ΔMRP1, L0ΔMRP2 was associated with an intracellular compartment, most likely endosomes. Co-expression with TMD0, however, resulted in apical localization of L0ΔMRP2 and transport activity. Uptake experiments with vesicles containing L0ΔMRP2 demonstrated that the molecule is able to transport LTC4. An MRP2 mutant without TMD0L0, ΔMRP2, was only core-glycosylated and localized intracellularly. Co-expression of ΔMRP2 with TMD0L0 resulted in an increased protein level of ΔMRP2, full glycosylation of the protein, routing to the apical membrane, and transport activity. Our results suggest that the TMD0 region is required for routing to or stable association with the apical membrane.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76032
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-760322
SN  - 0021-9258
VL  - 277.2002
IS  - 34
SP  - 31048
EP  - 31055
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -