Your browser doesn't support javascript.
loading
The Micronemal Plasmodium Proteins P36 and P52 Act in Concert to Establish the Replication-Permissive Compartment Within Infected Hepatocytes.
Arredondo, Silvia A; Swearingen, Kristian E; Martinson, Thomas; Steel, Ryan; Dankwa, Dorender A; Harupa, Anke; Camargo, Nelly; Betz, William; Vigdorovich, Vladimir; Oliver, Brian G; Kangwanrangsan, Niwat; Ishino, Tomoko; Sather, Noah; Mikolajczak, Sebastian; Vaughan, Ashley M; Torii, Motomi; Moritz, Robert L; Kappe, Stefan H I.
Afiliação
  • Arredondo SA; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, United States.
  • Swearingen KE; Institute for Systems Biology, Seattle, WA, United States.
  • Martinson T; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, United States.
  • Steel R; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, United States.
  • Dankwa DA; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, United States.
  • Harupa A; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, United States.
  • Camargo N; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, United States.
  • Betz W; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, United States.
  • Vigdorovich V; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, United States.
  • Oliver BG; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, United States.
  • Kangwanrangsan N; Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
  • Ishino T; Department of Molecular Parasitology, Proteo-Science Center, Ehime University, Shitsukawa, Toon, Japan.
  • Sather N; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, United States.
  • Mikolajczak S; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, United States.
  • Vaughan AM; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, United States.
  • Torii M; Department of Molecular Parasitology, Proteo-Science Center, Ehime University, Shitsukawa, Toon, Japan.
  • Moritz RL; Institute for Systems Biology, Seattle, WA, United States.
  • Kappe SHI; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, United States.
Article em En | MEDLINE | ID: mdl-30547015
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.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Protozoários / Hepatócitos / Esporozoítos / Malária Limite: Animals Idioma: En Revista: Front Cell Infect Microbiol Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Protozoários / Hepatócitos / Esporozoítos / Malária Limite: Animals Idioma: En Revista: Front Cell Infect Microbiol Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Suíça