Sarco/endoplasmic reticulum Ca2+ATPase type 3 isoforms (SERCA3b and SERCA3f): distinct roles in cell adhesion and ER stress.
Sarco/endoplasmic reticulum Ca(2+)ATPases (SERCAs) pump free Ca(2+) from the cytosol into the endoplasmic reticulum. The human SERCA3 family counts six members named SERCA3a to 3f. However, the exact role of these different isoforms in cellular physiology remains undetermined. In this study, we compared some physiological consequences of SERCA3b and SERCA3f overexpression in HEK-293 cells. We observed that overexpression of SERCA3b affected cell adhesion capacity associated with a major disorganization of F-actin and a decrease in focal adhesion. Furthermore, we found that SERCA3f overexpression resulted in an increase in endoplasmic reticulum stress markers (including processing of X-box-binding protein-1 (XBP-1) mRNA and expression of chaperone glucose-regulated protein 78 (GRP78)). This was associated with the activation of caspase cascade and a higher spontaneous cell death. In conclusion, these data point for the first time to distinct physiological roles of SERCA3 isoforms in cell functions.
Chaâbane
Chiraz
C
Inserm U.689 E4, IFR-139, Centre de Recherche Cardiovasculaire Inserm Lariboisière, Hôpital Lariboisière, Paris, France.
Corvazier
Elisabeth
E
Bredoux
Raymonde
R
Dally
Saoussen
S
Raïes
Aly
A
Villemain
Aude
A
Dupuy
Evelyne
E
Enouf
Jocelyne
J
Bobe
Régis
R
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics; D000091342:Endoplasmic Reticulum Chaperone BiP; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics; D009842:Oligopeptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012519:Sarcoplasmic Reticulum / Q000378:metabolism / Q000502:physiology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013997:Time Factors; D014157:Transcription Factors; D014162:Transfection; D000071717:X-Box Binding Protein 1
D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D007527:Isoenzymes; D009687:Nuclear Proteins; D009842:Oligopeptides; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506949:ATP2A3 protein, human; D000252:Calcium-Transporting ATPases