Calsenilin enhances apoptosis by altering endoplasmic reticulum calcium signaling.
Calsenilin (also called DREAM and KChIP3), a member of the neuronal calcium sensor family, was isolated in a yeast two-hybrid screen using an apoptotic domain of presenilin 2 as bait. Calsenilin is a cytoplasmic protein, but interacts with the COOH-termini of both presenilin 1 and presenilin 2 at the endoplasmic reticulum and the Golgi apparatus. In this study, we have investigated calsenilin's effect on apoptosis. In stable neuroglioma cell lines, we observed that calsenilin enhances apoptosis in response to serum withdrawal or thapsigargin. Consistent with these observations, caspase and apparently calpain activities were increased during apoptosis in calsenilin-overexpressing cells. Moreover, using calcium imaging we were able to show that cells treated with thapsigargin released more calcium from intracellular stores when calsenilin was overexpressed. Taken together, these data suggest that calsenilin causes cells to be more susceptible to apoptotic triggers, possibly by altering calcium dynamics.
Lilliehook
C
C
Laboratory of Molecular Neuropsychiatry, Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA.
Chan
S
S
Choi
E K
EK
Zaidi
N F
NF
Wasco
W
W
Mattson
M P
MP
Buxbaum
J D
JD
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology; D002154:Calpain / Q000187:drug effects / Q000378:metabolism; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D051605:Kv Channel-Interacting Proteins; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D012097:Repressor Proteins; D019284:Thapsigargin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D002135:Calcium-Binding Proteins; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; C496749:KCNIP3 protein, human; D051605:Kv Channel-Interacting Proteins; D012097:Repressor Proteins; D019284:Thapsigargin; D002154:Calpain; D020169:Caspases; D002118:Calcium