Trans-spliced Heat Shock Protein 90 Modulates Encystation in Giardia lamblia

Rishi Kumar Nageshan, Nainita Roy, Shatakshi Ranade, Utpal Tatu

PLoS Neglected Tropical Diseases (2014) 8(5): e2829

Speaker: Jia-Yan Wu (武珈言)                                     Time: 14:00~15:00, Nov. 19, 2014

Commentator: Dr. Shu-Ying Wang (王淑鶯 老師)   Place: Room 601

Abstract:

        Giardia lamblia, a flagellated protozoan parasite, is a common cause of diarrhea worldwide. On the average, Giardia migrates to the small intestine by digestive system of host after transmitted by contaminated food through fecal-oral route; simultaneously, Giardia converts into active trophozoite and causes pathogenesis of the disease. Moreover, some of the trophozoitesreleased by digestive system of host convert into cysts when encountering harsh environment. Nevertheless, the mechanism of transitions is unclear. In previous study, it shows that Heat shock protein 90 (Hsp90) which is a chaperone plays an important role in modulating transition from ring to trophozoite stage in Plasmodium [1]. Hence, the authors inferred whether Hsp90 modulates encystation in Giardia. First, the authors confirmed that there are independent transcripts, HspN, HspC and non-coding strand of the hypothetical gene, in the generation of the full length GlHsp90 through mass-spectrometric analysis. Hsp90 is an ATP dependent molecular chaperone, which requires binding and hydrolysis of ATP for maturation of the client proteins [2]. In ATPase assay, the binding data confirmed the ability of the trans-spliced Hsp90 to bind to its cognate ligand ATP. Moreover, the authors found that GlHsp90 is up-regulated in response to heat shock. Finally, the authors wanted to know how Hsp90 modulates encystation. On the one hand, GlHsp90 is down-regulated during encystations by qRT-PCR and western blot analysis. On the other hand, GIHsp90 induces encystations when inhibited by 17AAG. In conclusion, the authors implicated the trans-spliced GlHsp90 from Giardia to regulate an essential stage transition in the life cycle of this important human parasite; simultaneously, developing newer drugs will be aimed accurately at the unique molecules.

References:

1.    Banumathy, G., et al., Heat shock protein 90 function is essential for Plasmodium falciparum growth in human erythrocytes. J Biol Chem, 2003. 278(20): p. 18336-45.

2.    Meyer, P., et al., Structural and functional analysis of the middle segment of hsp90: implications for ATP hydrolysis and client protein and cochaperone interactions. Mol Cell, 2003. 11(3): p. 647-58.