Studying the calcium channels known as ORAI1
, ORAI2 and ORAI3 and their regulators STIM1 and STIM2 helps us to define ways to modulate immune responses for therapeutic use."
have demonstrated that deletion of the [Ca.sup.2+] channel Orai1
in pancreatic acinar cells ([Orai1.sup.-/-] mice) induces several signs of gut inflammation and bacterial overgrowth, leading to bacterial translocation, systemic infection, and death .
Variations in ORAI1
gene associated with Kawasaki disease.
Chiu et al., "Involvement of STIM1 and Orai1
in EGF-mediated cell growth in retinal pigment epithelial cells," Journal of Biomedical Science, vol.
Recently, a likely sensor for the luminal calcium concentration in the endoplasmic reticulum has been identified [47-49], and a second protein, Orai1
or CRACM, was identified as a modulator of CRAC ([Ca.sup.2+] release-activated [Ca.sup.2+] channels) or possibly the CRAC itself [50, 51].
Import occurs at the level of (i) cell plasma membrane through the calcium release-activated [Ca.sup.2+] channel protein 1 (ORAI1
), the store-operated calcium entry channels (SOCE), and specific receptor-operated channels (ROC) such as AMPA, NMDA, TRPC, and the voltage-dependent calcium channels (VDCC); (ii) endoplasmic reticulum (ER) through the sarco/endoplasmic reticulum calcium ATPase (SERCA); (iii) mitochondria intermembrane space through the voltage-dependent anion channel (VDAC); and (v) in the matrix by the mitochondrial uniporter (MCU), in synergy with the mitochondrial calcium uptake (MICU) system.
The working mechanisms affect modulation of the calcium channels Orai1
and TRPV3, as well as inhibiting mast cell activation.
After transfer, membranes were immunoblotted with the following primary antibodies: PMCA1, PMCA 4, and PMCA total (Affinity Bioreagents, Rockford, IL), SERCA 2 (Thermo Scientific, Pierce antibodies, Rockford, IL, USA), NCX1 (Swant, Bellinzona, Switzerland), STIM1 (Cell Signaling, Beverly, USA), Orai1
(Proteintech, USA), and IP3R1 (Millipore, USA).
Hogan said that they are not sure why, but theorized that septins rearrange the cellular membrane's structure to "corral" the key proteins STIM and ORAI1
, and maybe other factors needed for the calcium channel to operate.
Trebak, "Stim1 and orai1
mediate crac currents and store-operated calcium entry important for endothelial cell proliferation," Circulation Research, vol.
Peripheral/Central Localization of Orai1
Is Controlled by STIM1 upon UDP Stimulation.
Consequently, a calcium entry channel molecule (Orai1
) is activated by STIM1 and elicits store-operated calcium entry (SOCE).