Alzheimer’s disease-associated peptide Aβ₄₂ mobilizes ER Ca²⁺ via InsP₃R-dependent and -independent mechanisms

Jensen, Laura E.; Bultynck, Geert; Luyten, Tomas; Amijee, Hozeefa; Bootman, Martin D. and Roderick, H. Llewelyn (2013). Alzheimer’s disease-associated peptide Aβ₄₂ mobilizes ER Ca²⁺ via InsP₃R-dependent and -independent mechanisms. Frontiers in Molecular Neuroscience, 6, article no. 36.

DOI: https://doi.org/10.3389/fnmol.2013.00036

Abstract

Dysregulation of Ca²⁺ homeostasis is considered to contribute to the toxic action of the Alzheimer’s Disease (AD) associated Amyloid β-peptide (Aβ). Ca²⁺ fluxes across the plasma membrane and release from intracellular stores have both been reported to underlie the Ca²⁺ fluxes induced by Aβ₄₂. Here, we investigated the contribution of Ca²⁺ release from the endoplasmic reticulum (ER) to the effects of Aβ₄₂ upon Ca²⁺ homeostasis and the mechanism by which Aβ₄₂ elicited these effects. Consistent with previous reports, application of soluble oligomeric forms of Aβ₄₂ exhibited Ca²⁺ mobilizing properties. The Aβ₄₂-stimulated Ca²⁺ signals persisted in the absence of extracellular Ca²⁺ indicating a significant contribution of Ca²⁺ release from the ER Ca²⁺ store to the generation of these signals. Moreover, inositol 1,4,5-trisphosphate (InsP₃) signaling contributed to Aβ₄₂-stimulated Ca²⁺ release. The Ca²⁺ mobilizing effect of Aβ₄₂ was also observed when applied to permeabilized cells deficient in InsP₃ receptors revealing an additional direct effect of internalized Aβ₄₂ upon the ER, and a mechanism for induction of toxicity by intracellular Aβ₄₂.

Viewing alternatives

Metrics

Item Actions

Export

You can export this page using these formats Digital Object Identifier - DOI