Endoplasmic reticulum stress reduces the export from the ER and alters the architecture of post-ER compartments.
In eukaryotic cells several physiologic and pathologic conditions generate the accumulation of unfolded proteins in the endoplasmic reticulum (ER), leading to ER stress. To restore normal function, some ER transmembrane proteins sense the ER stress and activate coordinated signalling pathways collectively called the Unfolded Protein Response (UPR). Little is known on how the UPR relates to post-ER compartments and to the export from the ER of newly synthesized proteins. Here, we report that the ER stress response induced by either thapsigargin or nitric oxide modifies the dynamics of the intracellular distribution of ERGIC-53 and GM130, two markers of the ER Golgi Intermediate Compartment and of the cis-Golgi, respectively. In addition, induction of ER stress alters the morphology of the ERGIC and the Golgi complex and interferes with the reformation of both compartments. Moreover, ER stress rapidly reduces the transport to the Golgi complex of the temperature sensitive mutant of the Vesicular Stomatitis Virus G Glycoprotein (VSV-G) fused with the Green Fluorescent Protein (ts045G), without apparently decreasing the amount of the protein competent for export. Interestingly, a parallel rapid reduction of the number of Sec31 labelled fluorescent puncta on the ER membranes does occur, thus suggesting that the ER stress alters the ER export and the dynamic of post-ER compartments by rapidly targeting the formation of COPII-coated transport intermediates.
Amodio
Giuseppina
G
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Via Ponte Don Melillo, Fisciano-Salerno I-84034, Italy.
Renna
Maurizio
M
Paladino
Simona
S
Venturi
Consuelo
C
Tacchetti
Carlo
C
Moltedo
Ornella
O
Franceschelli
Silvia
S
Mallardo
Massimo
M
Bonatti
Stefano
S
Remondelli
Paolo
P
D001324:Autoantigens / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D022181:COP-Coated Vesicles / Q000187:drug effects / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002460:Cell Line; D022082:Cellular Structures / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004721:Endoplasmic Reticulum; D006056:Golgi Apparatus; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D015202:Protein Engineering; D021381:Protein Transport / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D019284:Thapsigargin / Q000494:pharmacology*; D056811:Unfolded Protein Response; D014759:Viral Envelope Proteins / Q000378:metabolism
D001324:Autoantigens; D015415:Biomarkers; C028391:G protein, vesicular stomatitis virus; C097741:Golgin subfamily A member 2; C084004:LMAN1 protein, human; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases