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Implication of different domains of the Leishmania major metacaspase in cell death and autophagy

Metacaspases (MCAs) are cysteine peptidases expressed in plants, fungi and protozoa, with a caspase-like histidine–cysteine catalytic dyad, but differing from caspases, for example, in their substrate specificity. The role of MCAs is subject to debate: roles in cell cycle control, in cell death or e...

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Autores principales: Casanova, M, Gonzalez, I J, Sprissler, C, Zalila, H, Dacher, M, Basmaciyan, L, Späth, G F, Azas, N, Fasel, N
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632311/
https://www.ncbi.nlm.nih.gov/pubmed/26492367
http://dx.doi.org/10.1038/cddis.2015.288
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author Casanova, M
Gonzalez, I J
Sprissler, C
Zalila, H
Dacher, M
Basmaciyan, L
Späth, G F
Azas, N
Fasel, N
author_facet Casanova, M
Gonzalez, I J
Sprissler, C
Zalila, H
Dacher, M
Basmaciyan, L
Späth, G F
Azas, N
Fasel, N
author_sort Casanova, M
collection PubMed
description Metacaspases (MCAs) are cysteine peptidases expressed in plants, fungi and protozoa, with a caspase-like histidine–cysteine catalytic dyad, but differing from caspases, for example, in their substrate specificity. The role of MCAs is subject to debate: roles in cell cycle control, in cell death or even in cell survival have been suggested. In this study, using a Leishmania major MCA-deficient strain, we showed that L. major MCA (LmjMCA) not only had a role similar to caspases in cell death but also in autophagy and this through different domains. Upon cell death induction by miltefosine or H(2)O(2), LmjMCA is processed, releasing the catalytic domain, which activated substrates via its catalytic dyad His/Cys and a proline-rich C-terminal domain. The C-terminal domain interacted with proteins, notably proteins involved in stress regulation, such as the MAP kinase LmaMPK7 or programmed cell death like the calpain-like cysteine peptidase. We also showed a new role of LmjMCA in autophagy, acting on or upstream of ATG8, involving Lmjmca gene overexpression and interaction of the C-terminal domain of LmjMCA with itself and other proteins. These results allowed us to propose two models, showing the role of LmjMCA in the cell death and also in the autophagy pathway, implicating different protein domains.
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spelling pubmed-46323112015-11-16 Implication of different domains of the Leishmania major metacaspase in cell death and autophagy Casanova, M Gonzalez, I J Sprissler, C Zalila, H Dacher, M Basmaciyan, L Späth, G F Azas, N Fasel, N Cell Death Dis Original Article Metacaspases (MCAs) are cysteine peptidases expressed in plants, fungi and protozoa, with a caspase-like histidine–cysteine catalytic dyad, but differing from caspases, for example, in their substrate specificity. The role of MCAs is subject to debate: roles in cell cycle control, in cell death or even in cell survival have been suggested. In this study, using a Leishmania major MCA-deficient strain, we showed that L. major MCA (LmjMCA) not only had a role similar to caspases in cell death but also in autophagy and this through different domains. Upon cell death induction by miltefosine or H(2)O(2), LmjMCA is processed, releasing the catalytic domain, which activated substrates via its catalytic dyad His/Cys and a proline-rich C-terminal domain. The C-terminal domain interacted with proteins, notably proteins involved in stress regulation, such as the MAP kinase LmaMPK7 or programmed cell death like the calpain-like cysteine peptidase. We also showed a new role of LmjMCA in autophagy, acting on or upstream of ATG8, involving Lmjmca gene overexpression and interaction of the C-terminal domain of LmjMCA with itself and other proteins. These results allowed us to propose two models, showing the role of LmjMCA in the cell death and also in the autophagy pathway, implicating different protein domains. Nature Publishing Group 2015-10 2015-10-22 /pmc/articles/PMC4632311/ /pubmed/26492367 http://dx.doi.org/10.1038/cddis.2015.288 Text en Copyright © 2015 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Casanova, M
Gonzalez, I J
Sprissler, C
Zalila, H
Dacher, M
Basmaciyan, L
Späth, G F
Azas, N
Fasel, N
Implication of different domains of the Leishmania major metacaspase in cell death and autophagy
title Implication of different domains of the Leishmania major metacaspase in cell death and autophagy
title_full Implication of different domains of the Leishmania major metacaspase in cell death and autophagy
title_fullStr Implication of different domains of the Leishmania major metacaspase in cell death and autophagy
title_full_unstemmed Implication of different domains of the Leishmania major metacaspase in cell death and autophagy
title_short Implication of different domains of the Leishmania major metacaspase in cell death and autophagy
title_sort implication of different domains of the leishmania major metacaspase in cell death and autophagy
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632311/
https://www.ncbi.nlm.nih.gov/pubmed/26492367
http://dx.doi.org/10.1038/cddis.2015.288
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