An accelerated activity of the GD3 synthase (ST8), with consequent GD3 accumulation, is part of the response to environmental stressors in different cell types. Depending on specific, yet largely undefined, cellular settings, this can be followed by adaptation or apoptosis, the latter mostly due to GD3-induced mitochondrial damage. Here we show that subcellular localization of ST8 could significantly affect the biological outcome of GD3 accumulation. Binding to the molecular chaperone calnexin causes the retention of ST8 within the endoplasmic reticulum ( ER) and prevents its relocalization to the Golgi. Calnexin-dependent ER retention does not affect the activity of ST8; yet the de novo synthesized GD3 largely fails to reach the mitochondria. Accordingly, overexpression of calnexin suppresses the pro-apoptotic activity of ST8, while the loss of calnexin sensitizes the cells to ST8-induced apoptosis. Reconstitution of calnexin confers protection to deficient cells. Thus, calnexin controls the biological outcome of GD3 accumulation and reveals a novel role in the stress response.

Tomassini, B., Malisan, F., Franchi, L., Nicolo, C., Calvo, G., Saito, T., et al. (2004). Calnexin suppresses GD3 synthase-induced apoptosis. THE FASEB JOURNAL, 18(13), 1553-1555 [10.1096/fj.04-1675fje].

Calnexin suppresses GD3 synthase-induced apoptosis

MALISAN, FLORENCE;TESTI, ROBERTO
2004-01-01

Abstract

An accelerated activity of the GD3 synthase (ST8), with consequent GD3 accumulation, is part of the response to environmental stressors in different cell types. Depending on specific, yet largely undefined, cellular settings, this can be followed by adaptation or apoptosis, the latter mostly due to GD3-induced mitochondrial damage. Here we show that subcellular localization of ST8 could significantly affect the biological outcome of GD3 accumulation. Binding to the molecular chaperone calnexin causes the retention of ST8 within the endoplasmic reticulum ( ER) and prevents its relocalization to the Golgi. Calnexin-dependent ER retention does not affect the activity of ST8; yet the de novo synthesized GD3 largely fails to reach the mitochondria. Accordingly, overexpression of calnexin suppresses the pro-apoptotic activity of ST8, while the loss of calnexin sensitizes the cells to ST8-induced apoptosis. Reconstitution of calnexin confers protection to deficient cells. Thus, calnexin controls the biological outcome of GD3 accumulation and reveals a novel role in the stress response.
2004
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/04 - PATOLOGIA GENERALE
English
Con Impact Factor ISI
apoptosis inducing factor; apoptosis inhibitor; calnexin; ceramide; ganglioside GD3; ganglioside GM3; mutant protein; protein Bax; synthetase; animal cell; apoptosis; article; cellular distribution; endoplasmic reticulum; enzyme repression; human; human cell; mitochondrion; morphological adaptation; nonhuman; priority journal; protein expression; protein localization; protein protein interaction; protein synthesis; stress; Animals; Apoptosis; Calnexin; Cell Line; Chickens; Cricetinae; Endoplasmic Reticulum; Golgi Apparatus; Humans; Mitochondria; Protein Transport; RNA, Messenger; Sialyltransferases; Animalia
Tomassini, B., Malisan, F., Franchi, L., Nicolo, C., Calvo, G., Saito, T., et al. (2004). Calnexin suppresses GD3 synthase-induced apoptosis. THE FASEB JOURNAL, 18(13), 1553-1555 [10.1096/fj.04-1675fje].
Tomassini, B; Malisan, F; Franchi, L; Nicolo, C; Calvo, G; Saito, T; Testi, R
Articolo su rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/31230
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