Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0021051 (
immunodeficiency
)
71,517
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
STIM1 is an endoplasmic reticulum (ER) protein that modulates the activity of a number of Ca
2+
transport systems. By direct physical interaction with ORAI1, a plasma membrane Ca
2+
channel, STIM1 activates the
I
CRAC
current, whereas the binding with the voltage-operated Ca
2+
channel Ca
V
1.2 inhibits the current through this latter channel. In this way, STIM1 is a key regulator of Ca
2+
signaling in excitable and non-excitable cells, and altered STIM1 levels have been reported to underlie several pathologies, including
immunodeficiency
, neurodegenerative diseases, and cancer. In both sporadic and familial Alzheimer's disease, a decrease of STIM1 protein levels accounts for the alteration of Ca
2+
handling that compromises neuronal cell viability. Using SH-SY5Y cells edited by CRISPR/Cas9 to knockout
STIM1
gene expression, this work evaluated the molecular mechanisms underlying the cell death triggered by the deficiency of STIM1, demonstrating that STIM1 is a positive regulator of
ITPR3
gene expression. ITPR3 (or IP3R3) is a Ca
2+
channel enriched at ER-mitochondria contact sites where it provides Ca
2+
for transport into the mitochondria. Thus, STIM1 deficiency leads to a strong reduction of
ITPR3
transcript and
ITPR3 protein
levels, a consequent decrease of the mitochondria free Ca
2+
concentration ([Ca
2+
]
mit
), reduction of mitochondrial oxygen consumption rate, and decrease in ATP synthesis rate. All these values were normalized by ectopic expression of ITPR3 in STIM1-KO cells, providing strong evidence for a new mode of regulation of [Ca
2+
]
mit
mediated by the STIM1-ITPR3 axis.
...
PMID:STIM1 Deficiency Leads to Specific Down-Regulation of ITPR3 in SH-SY5Y Cells. 3291 60
