Calnexin suppresses GD3 synthase-induced apoptosis.
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.
Laboratory of Immunology and Signal Transduction, Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Rome, Italy.
Barbara
B
Tomassini
Florence
F
Malisan
Luigi
L
Franchi
Chiara
C
Nicolò
Gloria Brea
GB
Calvo
Takashi
T
Saito
Roberto
R
Testi
D000818:Animals; D017209:Apoptosis; D037281:Calnexin / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002645:Chickens; D006224:Cricetinae; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012799:Sialyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D012333:RNA, Messenger; D037281:Calnexin; D012799:Sialyltransferases; C043662:alpha-N-acetylneuraminate alpha-2,8-sialyltransferase