LC3-association with the parasitophorous vacuole membrane of Plasmodium berghei liver stages follows a noncanonical autophagy pathway.

Wacker, Rahel Corina; Eickel, Nina; Schmuckli, Jacqueline; Annoura, Takeshi; Niklaus, Livia; Khan, Shahid M; Guan, Jun-Lin; Heussler, Volker (2017). LC3-association with the parasitophorous vacuole membrane of Plasmodium berghei liver stages follows a noncanonical autophagy pathway. Cellular microbiology, 19(10) Wiley 10.1111/cmi.12754

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Eukaryotic cells can employ autophagy to defend themselves against invading pathogens. Upon infection by Plasmodium berghei sporozoites, the host hepatocyte targets the invader by labelling the parasitophorous vacuole membrane (PVM) with the autophagy marker protein LC3. Until now, it has not been clear whether LC3 recruitment to the PVM is mediated by fusion of autophagosomes or by direct incorporation. To distinguish between these possibilities, we knocked out genes that are essential for autophagosome formation and for direct LC3 incorporation into membranes. The CRISPR/Cas9 system was employed to generate host cell lines deficient for either FIP200, a member of the initiation complex for autophagosome formation, or ATG5, responsible for LC3 lipidation and incorporation of LC3 into membranes. Infection of these knockout cell lines with P. berghei sporozoites revealed that LC3 recruitment to the PVM indeed depends on functional ATG5 and the elongation machinery, but not on FIP200 and the initiation complex, suggesting a direct incorporation of LC3 into the PVM. Importantly, in P. berghei-infected ATG5(-/-) host cells, lysosomes still accumulated at the PVM, indicating that the recruitment of lysosomes follows an LC3-independent pathway.

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:

Wacker, Rahel Corina; Eickel, Nina; Schmuckli, Jacqueline; Niklaus, Livia and Heussler, Volker

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1462-5814

Publisher:

Wiley

Funders:

[42] Schweizerischer Nationalfonds
[UNSPECIFIED] SystemsX

Language:

English

Submitter:

Volker Heussler

Date Deposited:

01 Dec 2017 13:59

Last Modified:

16 Jan 2019 15:23

Publisher DOI:

10.1111/cmi.12754

PubMed ID:

28573684

BORIS DOI:

10.7892/boris.107205

URI:

https://boris.unibe.ch/id/eprint/107205

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