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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Schmuckli PLoS One 2017.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (36MB) | Preview |
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) |
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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, 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: |
05 Dec 2022 15:08 |
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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