Pexophagy is a selective degradation pathway of peroxisomes. In the present study, we revealed that PpAtg21 was required for pexophagy in the methylotrophic yeast Pichia pastoris. PpAtg21 was essential for efficient lipidation of Atg8 and for de novo synthesis of pexophagic membranes. In contrast to PpAtg18, PpAtg21 was not necessary for vacuolar fission nor invagination during micropexophagy. PpAtg21 specifically bound to PI(3)P, but not to PI(3,5)P2 in vitro, and the localization analyses matched with this phosphoinositide-binding specificity. The mutant which lost the lipid-binding activity showed defect in pexophagy, suggesting that PI(3)P-binding activity of PpAtg21 was required for pexophagy.
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http://dx.doi.org/10.1111/1567-1364.12132 | DOI Listing |
Biomolecules
March 2023
Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), INSERM UMR-1297, Université Paul Sabatier, F-31432 Toulouse Cedex, France.
Phosphoinositides (PIs) play a crucial role in regulating intracellular signaling, actin cytoskeleton rearrangements, and membrane trafficking by binding to specific domains of effector proteins. They are primarily found in the membrane leaflets facing the cytosol. Our study demonstrates the presence of a pool of phosphatidylinositol 3-monophosphate (PI3P) in the outer leaflet of the plasma membrane of resting human and mouse platelets.
View Article and Find Full Text PDFEMBO J
April 2023
Department of Biochemistry, and Department of Thoracic Surgery of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
The cGAS-STING pathway plays an important role in host defense by sensing pathogen DNA, inducing type I IFNs, and initiating autophagy. However, the molecular mechanism of autophagosome formation in cGAS-STING pathway-induced autophagy is still unclear. Here, we report that STING directly interacts with WIPI2, which is the key protein for LC3 lipidation in autophagy.
View Article and Find Full Text PDFPlant Physiol
February 2023
Department of Plant Pathology, Nanjing Agricultural University, Nanjing 210095, China.
Oomycete pathogens secrete numerous effectors to manipulate plant immunity and promote infection. However, relatively few effector types have been well characterized. In this study, members of an FYVE domain-containing protein family that are highly expanded in oomycetes were systematically identified, and one secreted protein, PsFYVE1, was selected for further study.
View Article and Find Full Text PDFPLoS Pathog
November 2022
Eukaryotic Gene Expression Laboratory, National Institute of Immunology, New Delhi, India.
Phosphoinositides are important second messengers that regulate key cellular processes in eukaryotes. While it is known that a single phosphoinositol-3 kinase (PI3K) catalyses the formation of 3'-phosphorylated phosphoinositides (PIPs) in apicomplexan parasites like Plasmodium and Toxoplasma, how its activity and PI3P formation is regulated has remained unknown. Present studies involving a unique Vps15 like protein (TgVPS15) in Toxoplasma gondii provides insight into the regulation of phosphatidyl-3-phosphate (PI3P) generation and unravels a novel pathway that regulates parasite development.
View Article and Find Full Text PDFCells
March 2022
Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
Phosphatidylinositol-3-phosphate (PI3P), a major identity tag of early endosomes (EEs), provides a platform for the recruitment of numerous cellular proteins containing an FYVE or PX domain that is required for PI3P-dependent maturation of EEs. Most of the PI3P in EEs is generated by the activity of Vps34, a catalytic component of class III phosphatidylinositol-3-phosphate kinase (PI3Ks) complex. In this study, we analyzed the role of Vps34-derived PI3P in the EE recycling circuit of unperturbed cells using VPS34-IN1 (IN1), a highly specific inhibitor of Vps34.
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