Format

Send to

Choose Destination
See comment in PubMed Commons below
Channels (Austin). 2015;9(5):245-52. doi: 10.1080/19336950.2015.1071747. Epub 2015 Jul 28.

STIM and ORAI proteins in the nervous system.

Author information

1
a Carl-Ludwig-Institute for Physiology, University of Leipzig ; Leipzig , Germany.

Abstract

Stromal interaction molecules (STIM) 1 and 2 are sensors of the calcium concentration in the endoplasmic reticulum. Depletion of endoplasmic reticulum calcium stores activates STIM proteins which, in turn, bind and open calcium channels in the plasma membrane formed by the proteins ORAI1, ORAI2, and ORAI3. The resulting store-operated calcium entry (SOCE), mostly controlled by the principal components STIM1 and ORAI1, has been particularly characterized in immune cells. In the nervous system, all STIM and ORAI homologs are expressed. This review summarizes current knowledge on distribution and function of STIM and ORAI proteins in central neurons and glial cells, i.e. astrocytes and microglia. STIM2 is required for SOCE in hippocampal synapses and cortical neurons, whereas STIM1 controls calcium store replenishment in cerebellar Purkinje neurons. In microglia, STIM1, STIM2, and ORAI1 regulate migration and phagocytosis. The isoforms ORAI2 and ORAI3 are candidates for SOCE channels in neurons and astrocytes, respectively. Due to the role of SOCE in neuronal and glial calcium homeostasis, dysfunction of STIM and ORAI proteins may have consequences for the development of neurodegenerative disorders, such as Alzheimer's disease.

KEYWORDS:

CRAC; ORAI1; SOCE; STIM1; astrocytes; capacitative calcium entry; glia; microglia; neurons

PMID:
26218135
PMCID:
PMC4826113
DOI:
10.1080/19336950.2015.1071747
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Taylor & Francis Icon for PubMed Central
    Loading ...
    Support Center