Up-regulation of inositol 1,4,5-trisphosphate receptor type 1 is responsible for a decreased endoplasmic-reticulum Ca2+ content in presenilin double knock-out cells

Nadif Kasri, N., Kocks, S. L., Verbert, L., Hébert, S. S., Callewaert, G., Parys, J. B., Missiaen, L., De Smedt, H. (July 2006) Up-regulation of inositol 1,4,5-trisphosphate receptor type 1 is responsible for a decreased endoplasmic-reticulum Ca2+ content in presenilin double knock-out cells. Cell Calcium, 40 (1). pp. 41-51. ISSN 0143-4160 (Print)

URL: https://www.ncbi.nlm.nih.gov/pubmed/16675011
DOI: 10.1016/j.ceca.2006.03.005

Abstract

Presenilins (PS) are proteins involved in the pathogenesis of autosomal-dominant familial cases of Alzheimer's disease. Mutations in PS are known to induce specific alterations in cellular Ca2+ signaling which might be involved in the pathogenesis of neurodegenerative diseases. Mouse embryonic fibroblasts (MEF) deficient in PS1 and PS2 (PS DKO) as well as the latter rescued with PS1 (Rescue), were used to investigate the underlying mechanism of these alterations in Ca2+ signaling. PS DKO cells were characterized by a decrease in the [Ca2+]ER as measured by ER-targeted aequorin luminescence and an increased level of type 1 inositol 1,4,5-trisphosphate receptor (IP3R1). The lower [Ca2+]ER was associated with an increase in a Ca2+ leak from the ER. The increased IP3R1 expression and the concomitant changes in ER Ca2+ handling were reversed in the Rescue cells. Moreover using RNA-interference mediated reduction of IP3R1 we could demonstrate that the up-regulation of this isoform was responsible for the increased Ca2+ leak and the lowered [Ca2+]ER PS DKO cells. Finally, we show that the decreased [Ca2+]ER in PS DKO cells was protective against apoptosis.

Item Type: Paper
Uncontrolled Keywords: Animals Calcium metabolism Calcium Channels biosynthesis physiology Cells Cultured Endoplasmic Reticulum metabolism Membrane Proteins deficiency genetics Mice Mice Knockout Presenilin-1 Presenilin-2 Receptors Cytoplasmic Nuclear biosynthesis physiology Up-Regulation physiology
Subjects: diseases & disorders > mental disorders > delirium dementia cognitive disorders > Alzheimer's disease
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > PS proteins
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell signaling
organism description > animal > developmental stage > embryo
organism description > animal > mammal > rodent > mouse
CSHL Authors:
Communities: CSHL labs > Van Aelst lab
Depositing User: CSHL Librarian
Date: July 2006
Date Deposited: 13 Dec 2011 14:30
Last Modified: 27 Apr 2018 14:16
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22867

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