Nitric oxide-induced endoplasmic reticulum stress activates the expression of cargo receptor proteins and alters the glycoprotein transport to the Golgi complex.
The endoplasmic reticulum Golgi intermediate compartment 53 protein recycles continuously between the endoplasmic reticulum and the Golgi complex and ensures the anterograde transport of specific glycoproteins with the assistance of the Multiple Clotting Factor Deficiency adaptor protein. Therefore, to analyze the effect of the endoplasmic reticulum stress on the secretory pathway beyond the endoplasmic reticulum, we analyzed the expression of both proteins in J774 macrophages incubated with the nitric oxide donor DETA NONOate or with thapsigargin. Both proteins accumulated progressively, by a transcriptional mechanism, in response to these inducers. Nitric oxide also induced a higher level of calreticulin and glucose regulated 78 protein, two endoplasmic reticulum proteins controlled by the unfolded protein response. Interestingly, nitric oxide induced the processing of the activating transcription factor 6alpha of the unfolded protein response, while thapsigargin also induced the activation of the transcription factor X-box Binding Protein 1. In addition, we showed that the accumulation of both transporters occurred simultaneously with the activation of endoplasmic reticulum-stress-dependent apoptosis, suggesting that these proteins may participate in the events that will eventually decide the fate of the cell. Induction of endoplasmic reticulum stress affected the rate of anterograde transport of a reporter glycoprotein, indicating that the endoplasmic reticulum to Golgi transport is remarkably impaired. Our results indicate that increased levels of cargo receptor proteins might have a function either in the quality control of protein folding in the endoplasmic reticulum or in the homeostasis of the intermediate compartment and Golgi complex during cell stress.
Renna
Maurizio
M
Dipartimento di Biochimica e Biotecnologie Mediche, University of Naples Federico II, via S. Pansini 5, 1-80131 Naples, Italy.
Faraonio
Raffaella
R
Bonatti
Stefano
S
De Stefano
Daniela
D
Carnuccio
Rosa
R
Tajana
Gianfranco
G
Remondelli
Paolo
P
D051702:Activating Transcription Factor 6 / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000473:pathology*; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000378:metabolism*; D006056:Golgi Apparatus / Q000187:drug effects*; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D000071701:Regulatory Factor X Transcription Factors; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
D051702:Activating Transcription Factor 6; C497112:Atf6 protein, mouse; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C515307:ERGIC-53 protein, mouse; D006023:Glycoproteins; C515308:MCFD2 protein, mouse; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D009687:Nuclear Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D033921:Vesicular Transport Proteins; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D009569:Nitric Oxide; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D019284:Thapsigargin