regulation of store-operated calcium entry

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of store-operated calcium entry. [GOC:BHF]

Store-operated calcium entry (SOCE) is a crucial mechanism for maintaining intracellular calcium homeostasis in cells. It is triggered by depletion of calcium from the endoplasmic reticulum (ER), the primary intracellular calcium store. This depletion activates a signaling pathway that leads to the opening of plasma membrane calcium channels, allowing calcium influx from the extracellular environment.

The process involves several key players:

1. **Stromal interaction molecule 1 (STIM1) and STIM2:** These are transmembrane proteins located in the ER membrane that act as calcium sensors. When ER calcium levels decrease, STIM1 and STIM2 oligomerize and translocate to ER-plasma membrane junctions, where they interact with Orai channels.

2. **Orai1, Orai2, and Orai3:** These are transmembrane proteins that form the pore of the calcium channel in the plasma membrane. STIM1/2 activation leads to Orai channel opening, allowing calcium to flow into the cell.

3. **Calcium release-activated calcium (CRAC) channel:** This is the name given to the calcium channel formed by Orai proteins and activated by STIM1/2. It is highly selective for calcium ions and exhibits a unique characteristic of being highly sensitive to small changes in calcium concentration.

The following steps summarize the process of SOCE:

1. **ER calcium depletion:** Various stimuli can deplete ER calcium, including receptor activation, depletion of ATP, and activation of phospholipase C. This leads to a decrease in ER calcium concentration, triggering the activation of STIM1/2.

2. **STIM1/2 activation and oligomerization:** STIM1/2 proteins sense the decrease in ER calcium and undergo a conformational change, leading to their oligomerization and translocation to ER-plasma membrane junctions.

3. **Interaction with Orai channels:** At the junctions, STIM1/2 interact with Orai proteins, leading to their oligomerization and the formation of a functional CRAC channel.

4. **Calcium influx:** The opening of the CRAC channel allows calcium to flow from the extracellular environment into the cytoplasm, restoring calcium levels in the ER and replenishing the intracellular calcium pool.

5. **Feedback regulation:** Once calcium levels in the ER are restored, STIM1/2 dissociate from Orai channels, leading to the closure of the CRAC channel and the termination of calcium influx.

SOCE plays a critical role in various cellular functions, including muscle contraction, neurotransmitter release, hormone secretion, gene expression, cell proliferation, and immune responses. Dysregulation of SOCE has been implicated in several diseases, including autoimmune diseases, cardiovascular diseases, and cancer.'
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Proteins (2)

Compounds (5)