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Cysteine peptidases CPA and CPB are vital for autophagy and differentiation in Leishmania mexicana
Abstract
Summary: In the past, ultrastructural investigations of Leishmania mexicana amastigotes revealed structures that were tentatively identified as autophagosomes. This study has now provided definitive data that autophagy occurs in the parasite during differentiation both to metacyclic promastigotes and to amastigotes, autophagosomes being particularly numerous during metacyclic to amastigote form transformation. Moreover, the results demonstrate that inhibiting two major lysosomal cysteine peptidases (CPA and CPB) or removing their genes not only interferes with the autophagy pathway but also prevents metacyclogenesis and transformation to amastigotes, thus adding support to the hypothesis that autophagy is required for cell differentiation. The study suggests that L. mexicana CPA and CPB perform similar roles to the aspartic peptidase PEP4 and the serine peptidase PRB1 in Saccharomyces cerevisiae . The results also provide an explanation for why L. mexicana CPA/CPB‐deficient mutants transform to amastigotes very poorly and lack virulence in macrophages and mice.
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“Changes in the number of GFP-Atg8 puncta can also be monitored using flow cytometry (see Autophagic flux determination using flow and multispectral imaging cytometry) [384].”
From Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1 (2021) · cites this paper as [384]
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BackgroundPrelysosomal convergence of autophagic and endocytic pathways
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Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894
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Klionsky, D. J., Abdalla, F. C., Abeliovich, H., Abraham, R. T., Acevedo-Arozena, A., Adeli, K., Agholme, L., Agnello, M., Agostinis, P., Aguirre-Ghiso, J. A., et al. (2012) · Autophagy · doi:10.4161/auto.19496 · Cited by 3,996
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Metadata
- Authors
- Williams, R. A., Tetley, L., Mottram, J. C., & Coombs, G. H.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2006-06-27
- Volume
- 61
- Issue
- 3
- Pages
- 655-674
- ISSN
- 0950-382X
- 1365-2958
- Cited by
- 140
- References
- 4
- Language
- en
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