title: Familial Alzheimer's disease-linked presenilin-1 mutation M146V affects store-operated calcium entry: does gain look like loss?
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder that leads to neuron death and synapse loss in the hippocampus and cortex, with consequent cognitive disability and dementia. Mutations in the presenilin-1 (PS1) gene lead to familial Alzheimer's disease (FAD). Here, we report that the expression of FAD-linked PS1 M146V mutant affects store-operated calcium channel activity (Isoc) in human neuroblastoma SK-N-SH cells. Electrophysiological measurements and calcium imaging experiments have revealed the emergent role of calcium sensor STIM2 in the inhibition of calcium release-activated calcium channel activity (Icrac) and enhancement of intracellular Ca(2+) stores content due to PS1 M146V mutant expression. In general, the results of this study suggest that the pathological inhibition of one type of store-operated calcium channels caused by FAD PS1 mutant expression may be accounted for by preceding gain of spontaneous activity of store-operated calcium channels driven by STIM2.
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave, 194064 St. Petersburg, Russia. mariaandreevnar@gmail.com
authors.forename: M
authors.initials: M
authors.lastname: Ryazantseva
authors.forename: K
authors.initials: K
authors.lastname: Skobeleva
authors.forename: E
authors.initials: E
authors.lastname: Kaznacheyeva
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D009154:Mutation; D009447:Neuroblastoma / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics* / Q000378:metabolism; D000071738:Stromal Interaction Molecule 2; D014407:Tumor Cells, Cultured
chemical_list: D015815:Cell Adhesion Molecules; C508853:PSEN1 protein, human; D053764:Presenilin-1; C513279:STIM2 protein, human; D000071738:Stromal Interaction Molecule 2; D002118:Calcium