Systematic Identification of Plasmodium Falciparum Sporozoite Membrane Protein Interactions Reveals an Essential Role for the p24 Complex in Host Infection.

Autor:	Knöckel J; Cell Surface Signalling Laboratory, Wellcome Sanger Institute, Cambridge, United Kingdom; Malaria Programme, Wellcome Sanger Institute, Cambridge, United Kingdom., Dundas K; Cell Surface Signalling Laboratory, Wellcome Sanger Institute, Cambridge, United Kingdom; Malaria Programme, Wellcome Sanger Institute, Cambridge, United Kingdom., Yang ASP; Radboudumc Center for Infectious Diseases, Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands., Galaway F; Cell Surface Signalling Laboratory, Wellcome Sanger Institute, Cambridge, United Kingdom; Malaria Programme, Wellcome Sanger Institute, Cambridge, United Kingdom., Metcalf T; Malaria Programme, Wellcome Sanger Institute, Cambridge, United Kingdom., Gemert GV; Radboudumc Center for Infectious Diseases, Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands., Sauerwein RW; Radboudumc Center for Infectious Diseases, Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands., Rayner JC; Malaria Programme, Wellcome Sanger Institute, Cambridge, United Kingdom., Billker O; Malaria Programme, Wellcome Sanger Institute, Cambridge, United Kingdom; The Laboratory for Molecular Infection Medicine Sweden (MIMS) and Department of Molecular Biology, Umeå University, Umeå, Sweden., Wright GJ; Cell Surface Signalling Laboratory, Wellcome Sanger Institute, Cambridge, United Kingdom; Malaria Programme, Wellcome Sanger Institute, Cambridge, United Kingdom; Department of Biology, Hull York Medical School, York Biomedical Research Institute, University of York, York, United Kingdom. Electronic address: gw2@sanger.ac.uk.
Jazyk:	angličtina
Zdroj:	Molecular & cellular proteomics : MCP [Mol Cell Proteomics] 2021; Vol. 20, pp. 100038. Date of Electronic Publication: 2021 Jan 27.
DOI:	10.1074/mcp.RA120.002432
Abstrakt:	Sporozoites are a motile form of malaria-causing Plasmodium falciparum parasites that migrate from the site of transmission in the dermis through the bloodstream to invade hepatocytes. Sporozoites interact with many cells within the host, but the molecular identity of these interactions and their role in the pathology of malaria is poorly understood. Parasite proteins that are secreted and embedded within membranes are known to be important for these interactions, but our understanding of how they interact with each other to form functional complexes is largely unknown. Here, we compile a library of recombinant proteins representing the repertoire of cell surface and secreted proteins from the P. falciparum sporozoite and use an assay designed to detect extracellular interactions to systematically identify complexes. We identify three protein complexes including an interaction between two components of the p24 complex that is involved in the trafficking of glycosylphosphatidylinositol-anchored proteins through the secretory pathway. Plasmodium parasites lacking either gene are strongly inhibited in the establishment of liver-stage infections. These findings reveal an important role for the p24 complex in malaria pathogenesis and show that the library of recombinant proteins represents a valuable resource to investigate P. falciparum sporozoite biology. Competing Interests: Conflict of interest The authors declare no competing interests. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu