Contributed equally to this work.
Plasmodium yoelii inhibitor of cysteine proteases is exported to exomembrane structures and interacts with yoelipain-2 during asexual blood-stage development
Version of Record online: 14 MAR 2013
© 2013 John Wiley & Sons Ltd
Volume 15, Issue 9, pages 1508–1526, September 2013
How to Cite
Pei, Y., Miller, J. L., Lindner, S. E., Vaughan, A. M., Torii, M. and Kappe, S. H. I. (2013), Plasmodium yoelii inhibitor of cysteine proteases is exported to exomembrane structures and interacts with yoelipain-2 during asexual blood-stage development. Cellular Microbiology, 15: 1508–1526. doi: 10.1111/cmi.12124
- Issue online: 8 AUG 2013
- Version of Record online: 14 MAR 2013
- Accepted manuscript online: 20 FEB 2013 06:51AM EST
- Manuscript Accepted: 7 FEB 2013
- Manuscript Revised: 6 FEB 2013
- Manuscript Received: 19 SEP 2012
- R01 AI053709
Plasmodium falciparum (Pf) blood stages express falstatin, an inhibitor of cysteine proteases (ICP), which is implicated in regulating proteolysis during red blood cell infection. Recent data using the Plasmodium berghei rodent malaria model suggested an additional role for ICP in the infection of hepatocytes by sporozoites and during liver-stage development. Here we further characterize the role of ICP in vivo during infection with Plasmodium yoelii (Py) and Pf. We found that Py-ICP was refractory to targeted gene deletion indicating an essential function during asexual blood-stage replication, but significant downregulation of ICP using a regulated system did not impact blood-stage growth. Py-ICP localized to vesicles within the asexual blood-stage parasite cytoplasm, as well as the parasitophorous vacuole, and was exported to dynamic exomembrane structures in the infected RBC. In sporozoites, expression was observed in rhoptries, in addition to intracellular vesicles distinct from TRAP containing micronemes. During liver-stage development, Py-ICP was confined to the parasite compartment until the final phase of liver-stage development when, after parasitophorous vacuolemembrane breakdown, it was released into the infected hepatocyte. Finally, we identified the cysteine protease yoelipain-2 as a binding partner of Py-ICP during blood-stage infection. These data show that ICP may be important in regulating proteolytic processes during blood-stage development, and is likely playing a role in liver stage-hepatocyte interactions at the time of exoerythrocytic merozoite release.