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

M. Casanova, I. J. Gonzalez, C. Sprissler, H. Zalila, M. Dacher, L. Basmaciyan, G. F. Späth, N. Azas, N. Fasel

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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 incell 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 H2O2, 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.

Original languageEnglish
Article numbere1933
JournalCell Death and Disease
Volume6
Issue number10
DOIs
Publication statusPublished - 2015 Oct 1
Externally publishedYes

Fingerprint

Leishmania major
Autophagy
Cell Death
Caspases
Cysteine
miltefosine
Peptide Hydrolases
Proteins
Calpain
Substrate Specificity
Histidine
Proline
Catalytic Domain
Cell Survival
Fungi
Phosphotransferases
Genes

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

Casanova, M., Gonzalez, I. J., Sprissler, C., Zalila, H., Dacher, M., Basmaciyan, L., ... Fasel, N. (2015). Implication of different domains of the Leishmania major metacaspase in cell death and autophagy. Cell Death and Disease, 6(10), [e1933]. https://doi.org/10.1038/cddis.2015.288

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.

In: Cell Death and Disease, Vol. 6, No. 10, e1933, 01.10.2015.

Research output: Contribution to journalArticle

Casanova, M, Gonzalez, IJ, Sprissler, C, Zalila, H, Dacher, M, Basmaciyan, L, Späth, GF, Azas, N & Fasel, N 2015, 'Implication of different domains of the Leishmania major metacaspase in cell death and autophagy', Cell Death and Disease, vol. 6, no. 10, e1933. https://doi.org/10.1038/cddis.2015.288
Casanova M, Gonzalez IJ, Sprissler C, Zalila H, Dacher M, Basmaciyan L et al. Implication of different domains of the Leishmania major metacaspase in cell death and autophagy. Cell Death and Disease. 2015 Oct 1;6(10). e1933. https://doi.org/10.1038/cddis.2015.288
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. In: Cell Death and Disease. 2015 ; Vol. 6, No. 10.
@article{966b7a99c7244025aefb985ca8668cad,
title = "Implication of different domains of the Leishmania major metacaspase in cell death and autophagy",
abstract = "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 incell 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 H2O2, 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.",
author = "M. Casanova and Gonzalez, {I. J.} and C. Sprissler and H. Zalila and M. Dacher and L. Basmaciyan and Sp{\"a}th, {G. F.} and N. Azas and N. Fasel",
year = "2015",
month = "10",
day = "1",
doi = "10.1038/cddis.2015.288",
language = "English",
volume = "6",
journal = "Cell Death and Disease",
issn = "2041-4889",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Implication of different domains of the Leishmania major metacaspase in cell death and autophagy

AU - Casanova, M.

AU - Gonzalez, I. J.

AU - Sprissler, C.

AU - Zalila, H.

AU - Dacher, M.

AU - Basmaciyan, L.

AU - Späth, G. F.

AU - Azas, N.

AU - Fasel, N.

PY - 2015/10/1

Y1 - 2015/10/1

N2 - 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 incell 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 H2O2, 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.

AB - 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 incell 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 H2O2, 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.

UR - http://www.scopus.com/inward/record.url?scp=84975230168&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84975230168&partnerID=8YFLogxK

U2 - 10.1038/cddis.2015.288

DO - 10.1038/cddis.2015.288

M3 - Article

C2 - 26492367

AN - SCOPUS:84975230168

VL - 6

JO - Cell Death and Disease

JF - Cell Death and Disease

SN - 2041-4889

IS - 10

M1 - e1933

ER -