Evidence for activation of endogenous transporters in Xenopus laevis oocytes expressing the Plasmodium falciparum chloroquine resistance transporter, PfCRT

Nessler, Susanne, Friedrich, Oliver, Bakouh, Naziha, Fink, Rainer H. A., Sanchez, Cecilia P., Planelles, Gabrielle and Lanzer, Michael (2004) Evidence for activation of endogenous transporters in Xenopus laevis oocytes expressing the Plasmodium falciparum chloroquine resistance transporter, PfCRT. The Journal of Biological Chemistry, 279 38: 39438-39446. doi:10.1074/jbc.M404671200

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Author Nessler, Susanne
Friedrich, Oliver
Bakouh, Naziha
Fink, Rainer H. A.
Sanchez, Cecilia P.
Planelles, Gabrielle
Lanzer, Michael
Title Evidence for activation of endogenous transporters in Xenopus laevis oocytes expressing the Plasmodium falciparum chloroquine resistance transporter, PfCRT
Formatted title
Evidence for activation of endogenous transporters in Xenopus laevis oocytes expressing the Plasmodium falciparum chloroquine resistance transporter, PfCRT
Journal name The Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
1083-351X
Publication date 2004-09-17
Sub-type Article (original research)
DOI 10.1074/jbc.M404671200
Open Access Status File (Publisher version)
Volume 279
Issue 38
Start page 39438
End page 39446
Total pages 9
Editor Herbert Tabor
Place of publication Bethesda, MD, U.S.A.
Publisher American society for Biochemistry and Molecular Biology
Language eng
Subject 0601 Biochemistry and Cell Biology
0904 Chemical Engineering
Formatted abstract
A large body of genetic, reverse genetic, and epidemiological data has linked chloroquine-resistant malaria to polymorphisms within a gene termed pfcrt in the human malarial parasite Plasmodium falciparum. To investigate the biological function of the chloroquine resistance transporter, PfCRT, as well as its role in chloroquine resistance, we functionally expressed this protein in Xenopus laevis oocytes. Our data show that PfCRT-expressing oocytes exhibit a depolarized resting membrane potential and a higher intracellular pH compared with control oocytes. Pharmacological and electrophysiological studies link the higher intracellular pH to an enhanced amiloride-sensitive H+ extrusion and the low membrane potential to an activated nonselective cation conductance. The finding that both properties are independent of each other, together with the fact that they are endogenously present in X. laevis oocytes, supports a model in which PfCRT activates transport systems. Our data suggest that PfCRT plays a role as a direct or indirect activator or modulator of other transporters.
© 2004 by The American Society for Biochemistry and Molecular Biology, Inc.

Keyword Endogenous transporters
Polymorphisms
Plasmodium falciparum chloroquine resistance transporter
Xenopus laevis
Oocyte
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
 
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