The sarco/endoplasmic reticulum calcium-ATPase 2b is an endoplasmic reticulum stress-inducible protein.
The sarco/endoplasmic reticulum calcium-ATPase (SERCA) translocates Ca(2+) from the cytosol to the lumen of the endoplasmic reticulum. This Ca(2+) storage is important for cellular processes such as calcium signaling and endoplasmic reticulum (ER)-associated posttranslational protein modifications. We investigated the expression of the SERCA2 and SERCA3 isozymes in PC12 cells exposed to agents interfering with different aspects of the posttranslational protein processing within the ER, thereby activating the ER stress-induced unfolded protein response (UPR). All agents increased the SERCA2b mRNA level 3-4-fold, in parallel with increasing mRNA levels for the ER stress marker proteins BiP/GRP78 and CHOP/GADD153. In contrast, SERCA3 mRNA levels did not change. SERCA2b mRNA stability was not changed, indicating that the mechanism of its up-regulation was transcriptional, in accordance with the presence of ER stress response elements in the promoter region of the SERCA2 gene. SERCA2b was also increased at the protein level upon ER stress treatments. Induction of ER stress by tunicamycin, dithiothreitol, or l-azetidine 2-carboxylic acid did not result in depletion of ER calcium, showing that such depletion was not necessary for up-regulation of SERCA2b expression or UPR activation in general. We conclude that the SERCA2b expression can be controlled by the UPR pathway independently of ER Ca(2+) depletion.
Caspersen
C
C
Department of Medical Physiology and the Biotechnology Center for Cellular Communication, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
Pedersen
P S
PS
Treiman
M
M
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005786:Gene Expression Regulation; D018832:Molecular Chaperones / Q000378:metabolism; D016716:PC12 Cells; D011401:Promoter Regions, Genetic; D051381:Rats; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
C506948:Atp2a2 protein, rat; C506951:Atp2a3 protein, rat; D018832:Molecular Chaperones; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases