Document Detail

Upregulation of expression of the reticulocyte homology gene 4 in the Plasmodium falciparum clone Dd2 is associated with a switch in the erythrocyte invasion pathway.
MedLine Citation:
PMID:  16289357     Owner:  NLM     Status:  MEDLINE    
The Plasmodium falciparum clone, Dd2, that requires sialic acid for invasion can switch to a sialic acid independent pathway, Dd2(NM). To elucidate the molecular basis of the switch in invasion phenotype of Dd2 to Dd2(NM), we performed expression profiling of the parasites using an oligonucleotide microarray and real-time RT-PCR. We found that four genes were upregulated in Dd2(NM) by microarray analysis, only two of which could be confirmed by real time RT-PCR. One gene, PfRH4, is a member of the reticulocyte homology family and the other, PEBL, is a pseudogene of the Duffy binding-like family. The two genes are contiguous but transcribed in opposite directions. The DNA sequence of these ORFs, their 5'-intergenic region and a 1.1kb region 3' to each ORF are identical between Dd2 and Dd2(NM), suggesting that their transcription upregulation relates to transactivating factors. The transcription upregulation of PfRH4 was reflected at the protein level as PfRH4 protein expression was detected in Dd2(NM) and not in Dd2. Other sialic acid independent and dependent clones of P. falciparum showed variable transcript levels of PfRH4 and PEBL, unrelated to their dependence on sialic acid for invasion, suggesting that different P. falciparum clones use different receptors for sialic acid independent invasion. As Dd2(NM) is a selected subclone of Dd2, the marked upregulation of PfRH4 expression in Dd2(NM) suggests its role in erythrocyte invasion through the sialic acid independent pathway of Dd2(NM).
Deepak Gaur; Tetsuya Furuya; Jianbing Mu; Lu-bin Jiang; Xin-zhuan Su; Louis H Miller
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Publication Detail:
Type:  Journal Article     Date:  2005-10-25
Journal Detail:
Title:  Molecular and biochemical parasitology     Volume:  145     ISSN:  0166-6851     ISO Abbreviation:  Mol. Biochem. Parasitol.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-01-17     Completed Date:  2006-03-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8006324     Medline TA:  Mol Biochem Parasitol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  205-15     Citation Subset:  IM    
Laboratory of Malaria and Vector Research (LMVR), National Institutes of Allergy and Infectious Diseases/NIH, 12735 Twinbrook Parkway, Building Twinbrook III/Room 3E-32D, Bethesda, MD 20892-8132, USA.
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MeSH Terms
3' Flanking Region
Blotting, Western
DNA, Intergenic
Erythrocytes / parasitology
Gene Expression Profiling
Gene Expression Regulation*
Genes, Protozoan*
Membrane Proteins / analysis,  biosynthesis,  genetics*
Oligonucleotide Array Sequence Analysis
Plasmodium falciparum / genetics*,  pathogenicity,  physiology*
Protozoan Proteins / analysis,  biosynthesis,  genetics*
RNA, Messenger / analysis
RNA, Protozoan / analysis
Reverse Transcriptase Polymerase Chain Reaction
Sequence Analysis, DNA
Sialic Acids / metabolism
Reg. No./Substance:
0/DNA, Intergenic; 0/Membrane Proteins; 0/Protozoan Proteins; 0/RH4 protein, Plasmodium falciparum; 0/RNA, Messenger; 0/RNA, Protozoan; 0/Sialic Acids

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