TY - JOUR
T1 - Calsenilin enhances apoptosis by altering endoplasmic reticulum calcium signaling
AU - Lilliehook, C.
AU - Chan, S.
AU - Choi, E. K.
AU - Zaidi, N. F.
AU - Wasco, W.
AU - Mattson, M. P.
AU - Buxbaum, J. D.
N1 - Funding Information:
We thank Dr. R. Nixon for helpful advice with calpain activation, Drs. L. Pastorino and A. Ikin for stimulating discussions during the course of this work, and Dr. N. Haughey for advice on analyzing the calcium imaging data. The authors are grateful to the National Institutes of Health and the National Institute of Aging (AG15801 and AG05138 to J.D.B.) and to the Alzheimer’s Association (11RG-99-1508 to J.D.B.) for funding the study.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0036251786&partnerID=8YFLogxK
U2 - 10.1006/mcne.2001.1096
DO - 10.1006/mcne.2001.1096
M3 - Article
C2 - 11988022
AN - SCOPUS:0036251786
SN - 1044-7431
VL - 19
SP - 552
EP - 559
JO - Molecular and Cellular Neurosciences
JF - Molecular and Cellular Neurosciences
IS - 4
ER -