%A Arredondo,Silvia A. %A Swearingen,Kristian E. %A Martinson,Thomas %A Steel,Ryan %A Dankwa,Dorender A. %A Harupa,Anke %A Camargo,Nelly %A Betz,William %A Vigdorovich,Vladimir %A Oliver,Brian G. %A Kangwanrangsan,Niwat %A Ishino,Tomoko %A Sather,Noah %A Mikolajczak,Sebastian %A Vaughan,Ashley M. %A Torii,Motomi %A Moritz,Robert L. %A Kappe,Stefan H. I. %D 2018 %J Frontiers in Cellular and Infection Microbiology %C %F %G English %K Malaria,Plasmodium,Protein complex,invasion,Sporozoite,6-cys s48/45,microneme secretion,TRAP %Q %R 10.3389/fcimb.2018.00413 %W %L %M %P %7 %8 2018-November-27 %9 Original Research %# %! Plasmodium P36 and P52 act in concert to establish the PV %* %< %T The Micronemal Plasmodium Proteins P36 and P52 Act in Concert to Establish the Replication-Permissive Compartment Within Infected Hepatocytes %U https://www.frontiersin.org/articles/10.3389/fcimb.2018.00413 %V 8 %0 JOURNAL ARTICLE %@ 2235-2988 %X 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.