Artículo
Calreticulin-dimerization induced by post-translational arginylation is critical for stress granules scaffolding
Carpio, Marcos Alejandro
; Decca, Maria Belen
; López Sambrooks, Cecilia
; Durand, Edith Sandra
; Montich, Guillermo Gabriel
; Hallak, Marta Elena
Fecha de publicación:
04/2013
Editorial:
Elsevier
Revista:
International Journal Of Biochemistry And Cellular Biology
ISSN:
1357-2725
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Protein arginylation mediated by arginyl-tRNA protein transferase is a post-translational modification that occurs widely in biology, it has been shown to regulate protein and properties and functions. Post-translational arginylation is critical for embryogenesis, cardiovascular development and angiogenesis but the molecular effects of proteins arginylated in vivo are largely unknown. In the present study, we demonstrate that arginylation reduces CRT (calreticulin) thermostability and induces a greater degree of dimerization and oligomerization. R-CRT (arginylated calreticulin) forms disulfide-bridged dimers that are increased in low Ca2+ conditions at physiological temperatures, a similar condition to the cellular environment that it required for arginylation of CRT. Moreover, R-CRT self-oligomerizes through non-covalent interactions that are enhanced at temperatures above 40 °C, condition that mimics the heat shock treatment where R-CRT is the only isoespecies of CRT that associates in cells to SGs (stress granules). We show that in cells lacking CRT the scaffolding of larger SGs is impaired; the transfection with CRT (hence R-CRT expression) restores SGs assembly whereas the transfection with CRT mutated in Cys146 does not. Thus, R-CRT disulfide-bridged dimers (through Cys146) are essential for the scaffolding of larger SGs under heat shock, although these dimers are not required for R-CRT association to SGs. The alteration in SGs assembly is critical for the normal cellular recover of cells after heat induced stress. We conclude that R-CRT is emerging as a novel protein that has an impact on the regulation of SGs scaffolding and cell survival.
Palabras clave:
Calreticulin
,
Arginylation
,
Stress Granules
,
Dimerization
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Articulos(CIQUIBIC)
Articulos de CENTRO DE INVEST.EN QCA.BIOL.DE CORDOBA (P)
Articulos de CENTRO DE INVEST.EN QCA.BIOL.DE CORDOBA (P)
Citación
Carpio, Marcos Alejandro; Decca, Maria Belen; López Sambrooks, Cecilia; Durand, Edith Sandra; Montich, Guillermo Gabriel; et al.; Calreticulin-dimerization induced by post-translational arginylation is critical for stress granules scaffolding; Elsevier; International Journal Of Biochemistry And Cellular Biology; 45; 7; 4-2013; 1223-1235
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