Active APPL1 sequestration by Plasmodium favors liver-stage development.

Autor:	Lahree A; Instituto de Medicina Molecular- João Lobo Antunes (iMM-JLA), Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal; Departamento de Bioengenharia, Instituto Superior Técnico, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal., Baptista SJS; Instituto de Medicina Molecular- João Lobo Antunes (iMM-JLA), Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal., Marques S; Instituto de Medicina Molecular- João Lobo Antunes (iMM-JLA), Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal., Perschin V; Imaging Core Facility, Biocenter, University of Würzburg, 97074 Würzburg, Germany., Zuzarte-Luís V; Instituto de Medicina Molecular- João Lobo Antunes (iMM-JLA), Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal., Goel M; National Centre for Biological Sciences, Tata Institute of Fundamental Research (NCBS), Bellary Road, Bangalore 560065, Karnataka, India., Choudhary HH; CSIR-Central Drug Research Institute Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, Uttar Pradesh, India., Mishra S; CSIR-Central Drug Research Institute Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, Uttar Pradesh, India., Stigloher C; Imaging Core Facility, Biocenter, University of Würzburg, 97074 Würzburg, Germany., Zerial M; Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Pfotenhauerstraße 108, 01307 Dresden, Germany., Sundaramurthy V; National Centre for Biological Sciences, Tata Institute of Fundamental Research (NCBS), Bellary Road, Bangalore 560065, Karnataka, India., Mota MM; Instituto de Medicina Molecular- João Lobo Antunes (iMM-JLA), Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal. Electronic address: mmota@medicina.ulisboa.pt.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 May 31; Vol. 39 (9), pp. 110886.
DOI:	10.1016/j.celrep.2022.110886
Abstrakt:	Intracellular pathogens manipulate host cells to survive and thrive. Cellular sensing and signaling pathways are among the key host machineries deregulated to favor infection. In this study, we show that liver-stage Plasmodium parasites compete with the host to sequester a host endosomal-adaptor protein (APPL1) known to regulate signaling in response to endocytosis. The enrichment of APPL1 at the parasitophorous vacuole membrane (PVM) involves an atypical Plasmodium Rab5 isoform (Rab5b). Depletion of host APPL1 alters neither the infection nor parasite development; however, upon overexpression of a GTPase-deficient host Rab5 mutant (hRab5_Q79L), the parasites are smaller and their PVM is stripped of APPL1. Infection with the GTPase-deficient Plasmodium berghei Rab5b mutant (PbRab5b_Q91L) in this case rescues the PVM APPL1 signal and parasite size. In summary, we observe a robust correlation between the level of APPL1 retention at the PVM and parasite size during exoerythrocytic development. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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