The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
SERCA pump activity is physiologically regulated by presenilin and regulates amyloid β production
Open accessAbstract
In addition to disrupting the regulated intramembraneous proteolysis of key substrates, mutations in the presenilins also alter calcium homeostasis, but the mechanism linking presenilins and calcium regulation is unresolved. At rest, cytosolic Ca2+ is maintained at low levels by pumping Ca2+ into stores in the endoplasmic reticulum (ER) via the sarco ER Ca2+-ATPase (SERCA) pumps. We show that SERCA activity is diminished in fibroblasts lacking both PS1 and PS2 genes, despite elevated SERCA2b steady-state levels, and we show that presenilins and SERCA physically interact. Enhancing presenilin levels in Xenopus laevis oocytes accelerates clearance of cytosolic Ca2+, whereas higher levels of SERCA2b phenocopy PS1 overexpression, accelerating Ca2+ clearance and exaggerating inositol 1,4,5-trisphosphate–mediated Ca2+ liberation. The critical role that SERCA2b plays in the pathogenesis of Alzheimer's disease is underscored by our findings that modulating SERCA activity alters amyloid β production. Our results point to a physiological role for the presenilins in Ca2+ signaling via regulation of the SERCA pump.
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Citations
Cites
The versatility and universality of calcium signalling
Berridge, M. J., Lipp, P., & Bootman, M. D. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35036035 · Cited by 5,701
Cited by
Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease
Bezprozvanny, I., & Mattson, M. P. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.06.005 · Cited by 938
Targa Dias Anastacio, H., Matosin, N., & Ooi, L. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02024-7 · Cited by 401
PSEN1 Mutant iPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer's Disease
Oksanen, M., Petersen, A. J., Naumenko, N., Puttonen, K., Lehtonen, Š., Gubert Olivé, M., Shakirzyanova, A., Leskelä, S., Sarajärvi, T., Viitanen, M., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.10.016 · Cited by 332
Calcium signalling and Alzheimer's disease
Berridge, M. J. (2011) · Neurochemical Research · doi:10.1007/s11064-010-0371-4 · Cited by 167
Chami, L., & Checler, F. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-52 · Cited by 168
Metadata
- Authors
- Green, K. N., Demuro, A., Akbari, Y., Hitt, B. D., Smith, I. F., Parker, I., & LaFerla, F. M.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2008-06-30
- Volume
- 181
- Issue
- 7
- Pages
- 1107-1116
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2132682847
- Cited by
- 304
- References
- 1
- FWCI
- 17.49
- Type
- journal article
- Language
- en
- Open access
- hybrid
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