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Molecular & Biochemical Parasitology 150 (2006) 288299 Chloroquine-resistant isoforms of the Plasmodium falciparum chloroquine
 

Summary: Molecular & Biochemical Parasitology 150 (2006) 288299
Chloroquine-resistant isoforms of the Plasmodium falciparum chloroquine
resistance transporter acidify lysosomal pH in HEK293 cells more than
chloroquine-sensitive isoforms
David C. Reevesa,1, David A. Liebelta,1, Viswanathan Lakshmananb, Paul D. Roeped,
David A. Fidockb, Myles H. Akabasa,c,
a Department of Physiology and Biophysics, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, USA
b Department of Microbiology and Immunology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461, USA
c Department of Neuroscience and Medicine, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461, USA
d Department of Chemistry and of Biochemistry and Molecular Biology and the Lombardi Cancer Center,
Georgetown University, Washington, DC 20057, USA
Received 12 December 2005; received in revised form 31 August 2006; accepted 3 September 2006
Available online 25 September 2006
Abstract
The emergence of chloroquine-resistant Plasmodium falciparum malaria imperils the lives of millions of people in Africa, Southeast Asia
and South America. Chloroquine resistance is associated with mutations in the P. falciparum chloroquine resistance transporter (PfCRT). We
expressed chloroquine-sensitive (HB3) and resistant (Dd2) pfcrt alleles in HEK293 human embryonic kidney cells. PfCRT localized to the
lysosomal limiting membrane and was not detected in the plasma membrane. We observed significant acidification of lysosomes containing
PfCRT HB3 and Dd2, with Dd2 acidifying significantly more than HB3. A mutant HB3 allele expressing the K76T mutation (earlier found to
be key for chloroquine resistance) acidified to the same extent as Dd2, whereas the acidification by a Dd2 allele expressing the T76K "back

  

Source: Akabas, Myles - Department of Physiology and Biophysics, Albert Einstein College of Medicine, Yeshiva University

 

Collections: Biology and Medicine