Publication: The Micronemal Plasmodium Proteins P36 and P52 Act in Concert to Establish the Replication-Permissive Compartment Within Infected Hepatocytes
Issued Date
2018-01-01
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ISSN
22352988
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2-s2.0-85058768617
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Mahidol University
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SCOPUS
Bibliographic Citation
Frontiers in cellular and infection microbiology. Vol.8, (2018), 413
Suggested Citation
Silvia A. Arredondo, Kristian E. Swearingen, Thomas Martinson, Ryan Steel, Dorender A. Dankwa, Anke Harupa, Nelly Camargo, William Betz, Vladimir Vigdorovich, Brian G. Oliver, Niwat Kangwanrangsan, Tomoko Ishino, Noah Sather, Sebastian Mikolajczak, Ashley M. Vaughan, Motomi Torii, Robert L. Moritz, Stefan H.I. Kappe The Micronemal Plasmodium Proteins P36 and P52 Act in Concert to Establish the Replication-Permissive Compartment Within Infected Hepatocytes. Frontiers in cellular and infection microbiology. Vol.8, (2018), 413. doi:10.3389/fcimb.2018.00413 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/46065
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Title
The Micronemal Plasmodium Proteins P36 and P52 Act in Concert to Establish the Replication-Permissive Compartment Within Infected Hepatocytes
Author(s)
Silvia A. Arredondo
Kristian E. Swearingen
Thomas Martinson
Ryan Steel
Dorender A. Dankwa
Anke Harupa
Nelly Camargo
William Betz
Vladimir Vigdorovich
Brian G. Oliver
Niwat Kangwanrangsan
Tomoko Ishino
Noah Sather
Sebastian Mikolajczak
Ashley M. Vaughan
Motomi Torii
Robert L. Moritz
Stefan H.I. Kappe
Kristian E. Swearingen
Thomas Martinson
Ryan Steel
Dorender A. Dankwa
Anke Harupa
Nelly Camargo
William Betz
Vladimir Vigdorovich
Brian G. Oliver
Niwat Kangwanrangsan
Tomoko Ishino
Noah Sather
Sebastian Mikolajczak
Ashley M. Vaughan
Motomi Torii
Robert L. Moritz
Stefan H.I. Kappe
Abstract
Within the liver, Plasmodium sporozoites traverse cells searching for a "suitable" hepatocyte, invading these cells through a process that results in the formation of a parasitophorous vacuole (PV), within which the parasite undergoes intracellular replication as a liver stage. It was previously established that two members of the Plasmodium s48/45 protein family, P36 and P52, are essential for productive invasion of host hepatocytes by sporozoites as their simultaneous deletion results in growth-arrested parasites that lack a PV. Recent studies point toward a pathway of entry possibly involving the interaction of P36 with hepatocyte receptors EphA2, CD81, and SR-B1. However, the relationship between P36 and P52 during sporozoite invasion remains unknown. Here we show that parasites with a single P52 or P36 gene deletion each lack a PV after hepatocyte invasion, thereby pheno-copying the lack of a PV observed for the P52/P36 dual gene deletion parasite line. This indicates that both proteins are equally important in the establishment of a PV and act in the same pathway. We created a Plasmodium yoelii P36mCherry tagged parasite line that allowed us to visualize the subcellular localization of P36 and found that it partially co-localizes with P52 in the sporozoite secretory microneme organelles. Furthermore, through co-immunoprecipitation studies in vivo, we determined that P36 and P52 form a protein complex in sporozoites, indicating a concerted function for both proteins within the PV formation pathway. However, upon sporozoite stimulation, only P36 was released as a secreted protein while P52 was not. Our results support a model in which the putatively glycosylphosphatidylinositol (GPI)-anchored P52 may serve as a scaffold to facilitate the interaction of secreted P36 with the host cell during sporozoite invasion of hepatocytes.