SERCA pump activity is physiologically regulated by presenilin and regulates amyloid β production

Autor: Kim N. Green, Brian D. Hitt, Yama Akbari, Ian F. Smith, Angelo Demuro, Frank M. LaFerla, Ian Parker
Rok vydání: 2008
Předmět:
Physiology
Xenopus
Inositol 1
4
5-Trisphosphate
Endoplasmic Reticulum
Mice
chemistry.chemical_compound
Cytosol
0302 clinical medicine
Cricetinae
Inositol
Enzyme Inhibitors
Research Articles
Mice
Knockout
0303 health sciences
biology
Cell biology
Protein Transport
cardiovascular system
Protein Binding
medicine.medical_specialty
SERCA
Amyloid
chemistry.chemical_element
CHO Cells
Calcium
Article
Presenilin
Sarcoplasmic Reticulum Calcium-Transporting ATPases
03 medical and health sciences
Cricetulus
Alzheimer Disease
Internal medicine
Presenilin-2
mental disorders
Presenilin-1
medicine
Animals
Humans
030304 developmental biology
Amyloid beta-Peptides
Endoplasmic reticulum
Cell Biology
Fibroblasts
biology.organism_classification
nervous system diseases
Endocrinology
Amino Acid Substitution
chemistry
Mutation
030217 neurology & neurosurgery
Zdroj: The Journal of Cell Biology
Green, KN; Demuro, A; Akbari, Y; Hitt, BD; Smith, IF; Parker, I; et al.(2008). SERCA pump activity is physiologically regulated by presenilin and regulates amyloid β production. Journal of Cell Biology, 181(7), 1107-1116. doi: 10.1083/jcb.200706171. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/1489j8qc
ISSN: 1540-8140
0021-9525
Popis: 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 Ca 2+ 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. © 2008 Green et al. The Rockefeller University Press.
Databáze: OpenAIRE
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