Inverted recruitment of autophagy proteins to the Plasmodium berghei parasitophorous vacuole membrane.

Schmuckli, Jacqueline; Reber, Vera; Wacker, Rahel Corina; Bindschedler, Annina; Zakher, Anthony; Heussler, Volker (2017). Inverted recruitment of autophagy proteins to the Plasmodium berghei parasitophorous vacuole membrane. PLoS ONE, 12(8), e0183797. Public Library of Science 10.1371/journal.pone.0183797

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Selective autophagy and related mechanisms can act as variable defense mechanisms against pathogens and can therefore be considered as intracellular immune responses. When in hepatocytes, Plasmodium parasites reside in a parasitophorous vacuole (PV) and the PV membrane (PVM) is the main contact site between host cell and parasite. Early in infection, the PVM is directly labeled with host cell autophagy proteins LC3B and p62 (nucleoporin 62). We investigated the recruitment of different selective autophagy receptors and could show that mainly p62 and NBR1 (neighbour of BRCA1 gene 1) and to a lesser extent NDP52 (nuclear dot protein 52) associate with the PVM. To investigate the recruitment of these receptors to the PVM in Plasmodium-infected cells, we generated LC3B knock out HeLa cells. In these cell lines, autophagosome formation and autophagic flux are not different to those in WT cells. Unexpectedly, p62 and NBR1 recruitment to the PVM was strongly impaired in LC3B-negative host cells, suggesting that LC3B recruits both receptors to the PVM of Plasmodium parasites. We also noticed that LC3B recruited ubiquitin to the PVM. This indicates that, in comparison to classical selective autophagy, in P. berghei-infected cells the order of membrane labeling with autophagy proteins appears to be inverted from canonical ubiquitin-receptor-LC3B recruitment to LC3B-receptor and possibly ubiquitin.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology > Malaria
08 Faculty of Science > Department of Biology > Institute of Cell Biology
09 Interdisciplinary Units > Microscopy Imaging Center (MIC)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Schmuckli, Jacqueline; Reber, Vera; Wacker, Rahel Corina; Zakher, Anthony and Heussler, Volker

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

1932-6203

Publisher:

Public Library of Science

Funders:

[42] Schweizerischer Nationalfonds
[UNSPECIFIED] Systems X

Language:

English

Submitter:

Volker Heussler

Date Deposited:

01 Dec 2017 10:38

Last Modified:

25 Oct 2019 06:00

Publisher DOI:

10.1371/journal.pone.0183797

PubMed ID:

28841718

BORIS DOI:

10.7892/boris.107204

URI:

https://boris.unibe.ch/id/eprint/107204

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