Τίτλος:
Calcium regulates the interaction of amyloid precursor protein with Homer3 protein
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Ca2+ dysregulation is an important factor implicated in Alzheimer's disease pathogenesis. The mechanisms mediating the reciprocal regulation of Ca2+ homeostasis and amyloid precursor protein (APP) metabolism, function, and protein interactions are not well known. We have previously shown that APP interacts with Homer proteins, which inhibit APP processing toward amyloid-β. In this study, we investigated the effect of Ca2+ homeostasis alterations on APP/Homer3 interaction. Influx of extracellular Ca2+ upon treatment of HEK293cells with the ionophore A23187 or addition of extracellular Ca2+ in cells starved of calcium specifically reduced APP/Homer3 but not APP/X11a interaction. Endoplasmic reticulum Ca2+ store depletion by thapsigargin followed by store-operated calcium entry also decreased the interaction. Interestingly, application of a phospholipase C stimulator, which causes inositol 1,4,5-trisphosphate-induced endoplasmic reticulum Ca2+ release, caused dissociation of APP/Homer3 complex. In human neuroblastoma cells, membrane depolarization also disrupted the interaction. This is the first study showing that changes in Ca2+ homeostasis affect APP protein interactions. Our results suggest that Ca2+ and Homers play a significant role in the development of Alzheimer's disease pathology. © 2014.
Συγγραφείς:
Kyratzi, E.
Efthimiopoulos, S.
Περιοδικό:
Neurobiology of Aging
Εκδότης:
ELSEVIER SCIENCE INC 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
Λέξεις-κλειδιά:
amyloid precursor protein; calcimycin; calcium; calcium ion; cytoplasm protein; inositol 1,4,5 trisphosphate; phospholipase C; protein homer 3; thapsigargin; unclassified drug; X11a protein; amyloid precursor protein; calcimycin; calcium; calcium ionophore; carrier protein; protein binding; protein homer; thapsigargin, article; calcium depletion; calcium homeostasis; calcium transport; complex formation; controlled study; dissociation; endoplasmic reticulum; extracellular calcium; HEK293 cell line; human; human cell; membrane depolarization; neuroblastoma cell; priority journal; protein protein interaction; Alzheimer disease; drug effects; genetics; membrane potential; metabolism; neuroblastoma; physiology; tumor cell culture, Alzheimer Disease; Amyloid beta-Protein Precursor; Calcimycin; Calcium; Calcium Ionophores; Carrier Proteins; Endoplasmic Reticulum; HEK293 Cells; Humans; Membrane Potentials; Neuroblastoma; Protein Binding; Thapsigargin; Tumor Cells, Cultured
DOI:
10.1016/j.neurobiolaging.2014.03.019
