%0 Journal Article
%T Upregulation of the SERCA-type Ca2+ pump activity in response to endoplasmic reticulum stress in PC12 cells
%A Annette H£żjmann Larsen
%A Aase Frandsen
%A Marek Treiman
%J BMC Biochemistry
%D 2001
%I BioMed Central
%R 10.1186/1471-2091-2-4
%X We show here that in PC12 cells, depletion of ER Ca2+ by EGTA, as well as inhibition of disulphide bridge formation within the ER by dithiotreitol or inhibition of N-glycosylation by tunicamycin, led to a 2- to 3-fold increase of the SERCA-mediated 45Ca2+ transport to microsomes isolated from cells exposed to these stress agents. The time course of this response corresponded to that for transcriptional upregulation of ER stress proteins, as well as to the increase in the SERCA2b mRNA, as we recently observed in an independent study.These findings provide the first functional evidence for the increase of SERCA pumping capacity in cells subjected to the ER stress. Since at least three different and unrelated mechanisms of eliciting the ER stress response were found to cause this functional upregulation of Ca2+ transport into the ER, these results support the existence of a coupling between the induction of the UPR pathway in general, and the regulation of expression of at least one of the SERCA pump isoforms.Endoplasmic reticulum (ER) is a compartment simultaneously involved in the processes of protein synthesis and Ca2+ homeostasis in eukaryotic cells. Nascent polypeptide chains entering the secretory pathway, as well as extracytosolic portions of proteins destined for the external or internal cell membranes, translocate into the ER lumen. Within the ER, posttranslational processes including folding, glycosylation, subunit assembly and transfer to the Golgi compartment take place, assisted by chaperone proteins residing in the ER lumen [1,2]. In addition, proper protein folding and maturation depends on the maintenance of the oxidative milieu and high Ca2+ concentrations within the ER [3-5]. Reducing agents, depletion of ER lumenal Ca2+, inhibition of glycosylation or interference with the secretory pathway (by preventing transfer to the Golgi system), each lead to an accumulation of misfolded protein intermediates and increase the demand on the chaperoning capacity.
%U http://www.biomedcentral.com/1471-2091/2/4