DOI: 10.1073/pnas.97.15.8590. Calsenilin reverses presenilin-mediated enhancement of calcium signaling

Calsenilin reverses presenilin-mediated enhancement of calcium signaling

10.1073/pnas.97.15.8590

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Most cases of autosomal-dominant familial Alzheimer's disease are linked to mutations in the presenilin genes ( PS1 and PS2 ). In addition to modulating β-amyloid production, presenilin mutations also produce highly specific and selective alterations in intracellular calcium signaling. Although the molecular mechanisms underlying these changes are not known, one candidate molecular mediator is calsenilin, a recently identified calcium-binding protein that associates with the C terminus of both PS1 and PS2. In this study, we investigated the effects of calsenilin on calcium signaling in Xenopus oocytes expressing either wild-type or mutant PS1. In this system, mutant PS1 potentiated the amplitude of calcium signals evoked by inositol 1,4,5-trisphosphate and also accelerated their rates of decay. We report that calsenilin coexpression reverses both of these potentially pathogenic effects. Notably, expression of calsenilin alone had no discernable effects on calcium signaling, suggesting that calsenilin modulates these signals by a mechanism independent of simple calcium buffering. Our findings further suggest that the effects of presenilin mutations on calcium signaling are likely mediated through the C-terminal domain, a region that has also been implicated in the modulation of β-amyloid production and cell death.

Bibliography

Leissring, M. A., Yamasaki, T. R., Wasco, W., Buxbaum, J. D., Parker, I., & LaFerla, F. M. (2000). Calsenilin reverses presenilin-mediated enhancement of calcium signaling. Proceedings of the National Academy of Sciences, 97(15), 8590â8593.

Authors 6

Malcolm A. Leissring (first)
Tritia R. Yamasaki (additional)
Wilma Wasco (additional)
Joseph D. Buxbaum (additional)
Ian Parker (additional)
Frank M. LaFerla (additional)

References 30 Referenced 73

10.1038/399a023
10.1046/j.1471-4159.1999.0721061.x
10.1074/jbc.274.46.32535
10.1097/00001756-199612200-00074
10.1038/4789
10.1073/pnas.91.2.534
10.1016/0024-3205(96)00327-X
10.1006/nbdi.1998.0176
10.1021/bi00181a016
10.1007/BF03159951
10.1046/j.1471-4159.1998.70010001.x
10.1038/2673
T-W Kim, W P Pettingell, R E Tanzi Soc Neurosci Abstr 24, 757, (abstr.). (1998). / Soc Neurosci Abstr by Kim T-W (1998)
10.1016/0014-5793(94)01338-2
10.1074/jbc.273.30.18930
10.1038/35000592
10.1038/18044
10.1101/SQB.1996.061.01.055
I Parker Neuromethods: Intracellular Messengers, eds A Boulton, C W Taylor (Humana, Totowa, NJ) 20, 369–393 (1992). (10.1385/0-89603-207-8:369) / Neuromethods: Intracellular Messengers by Parker I (1992)
10.1016/S0076-6879(98)91024-2
10.1111/j.1469-7793.1998.067bo.x
10.1006/exnr.1996.6348
10.1016/S0896-6273(00)80291-3
10.1038/351751a0
10.1083/jcb.149.4.793
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10.1073/pnas.95.6.3227
10.1523/JNEUROSCI.19-24-10627.1999
10.1074/jbc.271.49.31025

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:32 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 5:30 p.m.)
Indexed	3 weeks, 2 days ago (Aug. 7, 2025, 4:51 a.m.)
Issued	25 years, 1 month ago (July 18, 2000)
Published	25 years, 1 month ago (July 18, 2000)
Published Online	25 years, 1 month ago (July 18, 2000)
Published Print	25 years, 1 month ago (July 18, 2000)

Funders 0

None

BibTeX

@article{Leissring_2000, title={Calsenilin reverses presenilin-mediated enhancement of calcium signaling}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.97.15.8590}, DOI={10.1073/pnas.97.15.8590}, number={15}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Leissring, Malcolm A. and Yamasaki, Tritia R. and Wasco, Wilma and Buxbaum, Joseph D. and Parker, Ian and LaFerla, Frank M.}, year={2000}, month=jul, pages={8590–8593} }

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