• Two Plasmodium 6-Cys family-related proteins have distinct and critical roles in liver-stage development.

Two Plasmodium 6-Cys family-related proteins have distinct and critical roles in liver-stage development.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2014-02-11)
Takeshi Annoura, Ben C L van Schaijk, Ivo H J Ploemen, Mohammed Sajid, Jing-wen Lin, Martijn W Vos, Avinash G Dinmohamed, Daniel K Inaoka, Sanna R Rijpma, Geert-Jan van Gemert, Severine Chevalley-Maurel, Szymon M Kiełbasa, Fay Scheltinga, Blandine Franke-Fayard, Onny Klop, Cornelus C Hermsen, Kiyoshi Kita, Audrey Gego, Jean-Francois Franetich, Dominique Mazier, Stephen L Hoffman, Chris J Janse, Robert W Sauerwein, Shahid M Khan

The 10 Plasmodium 6-Cys proteins have critical roles throughout parasite development and are targets for antimalaria vaccination strategies. We analyzed the conserved 6-cysteine domain of this family and show that only the last 4 positionally conserved cysteine residues are diagnostic for this domain and identified 4 additional "6-Cys family-related" proteins. Two of these, sequestrin and B9, are critical to Plasmodium liver-stage development. RT-PCR and immunofluorescence assays show that B9 is translationally repressed in sporozoites and is expressed after hepatocyte invasion where it localizes to the parasite plasma membrane. Mutants lacking B9 expression in the rodent malaria parasites P. berghei and P. yoelii and the human parasite P. falciparum developmentally arrest in hepatocytes. P. berghei mutants arrest in the livers of BALB/c (100%) and C57BL6 mice (>99.9%), and in cultures of Huh7 human-hepatoma cell line. Similarly, P. falciparum mutants while fully infectious to primary human hepatocytes abort development 3 d after infection. This growth arrest is associated with a compromised parasitophorous vacuole membrane a phenotype similar to, but distinct from, mutants lacking the 6-Cys sporozoite proteins P52 and P36. Our results show that 6-Cys proteins have critical but distinct roles in establishment and maintenance of a parasitophorous vacuole and subsequent liver-stage development.

Product Number
Product Description

L-Cysteine, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
L-Cysteine, BioUltra, ≥98.5% (RT)
L-Cysteine, produced by Wacker Chemie AG, Burghausen, Germany, ≥98.0%
L-Cysteine, from non-animal source, BioReagent, suitable for cell culture, ≥98%
L-Cysteine, 97%
L-Cysteine, ≥97%, FG