Sorcin is an early marker of neurodegeneration, Ca
Animals
Biomarkers, Tumor
/ metabolism
Calcium Signaling
Calcium-Binding Proteins
/ biosynthesis
Cell Line, Tumor
Cells, Cultured
Endoplasmic Reticulum
/ metabolism
Endoplasmic Reticulum Stress
HeLa Cells
Humans
Mice
Neurodegenerative Diseases
/ metabolism
Neurons
/ metabolism
Ryanodine Receptor Calcium Release Channel
/ metabolism
Transfection
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
15 10 2020
15 10 2020
Historique:
received:
02
12
2019
accepted:
18
09
2020
revised:
16
09
2020
entrez:
16
10
2020
pubmed:
17
10
2020
medline:
14
5
2021
Statut:
epublish
Résumé
Dysregulation of calcium signaling is emerging as a key feature in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), and targeting this process may be therapeutically beneficial. Under this perspective, it is important to study proteins that regulate calcium homeostasis in the cell. Sorcin is one of the most expressed calcium-binding proteins in the human brain; its overexpression increases endoplasmic reticulum (ER) calcium concentration and decreases ER stress in the heart and in other cellular types. Sorcin has been hypothesized to be involved in neurodegenerative diseases, since it may counteract the increased cytosolic calcium levels associated with neurodegeneration. In the present work, we show that Sorcin expression levels are strongly increased in cellular, animal, and human models of AD, PD, and HD, vs. normal cells. Sorcin partially colocalizes with RyRs in neurons and microglia cells; functional experiments with microsomes containing high amounts of RyR2 and RyR3, respectively, show that Sorcin is able to regulate these ER calcium channels. The molecular basis of the interaction of Sorcin with RyR2 and RyR3 is demonstrated by SPR. Sorcin also interacts with other ER proteins as SERCA2 and Sigma-1 receptor in a calcium-dependent fashion. We also show that Sorcin regulates ER calcium transients: Sorcin increases the velocity of ER calcium uptake (increasing SERCA activity). The data presented here demonstrate that Sorcin may represent both a novel early marker of neurodegenerative diseases and a response to cellular stress dependent on neurodegeneration.
Identifiants
pubmed: 33060591
doi: 10.1038/s41419-020-03063-y
pii: 10.1038/s41419-020-03063-y
pmc: PMC7566454
doi:
Substances chimiques
Biomarkers, Tumor
0
Calcium-Binding Proteins
0
RYR1 protein, human
0
RYR3 protein, human
0
RyR2 protein, human
0
Ryanodine Receptor Calcium Release Channel
0
SRI protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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