activation of store-operated calcium channel activity

Definition

Target type: biologicalprocess

A process that initiates the activity of an inactive store-operated calcium channel. [GOC:mah]

Store-operated calcium channels (SOCs) are a critical component of calcium signaling pathways that regulate a wide range of cellular functions, including gene expression, muscle contraction, and neurotransmitter release. These channels are activated by depletion of calcium from intracellular stores, primarily the endoplasmic reticulum (ER), a process that initiates a chain of events leading to calcium influx from the extracellular space. The key players in this activation process are:

1. **Stromal interaction molecule 1 (STIM1) and STIM2:** These proteins act as sensors of ER calcium levels and are embedded in the ER membrane. When ER calcium levels decrease, STIM1 and STIM2 undergo conformational changes, causing them to oligomerize and translocate to ER-plasma membrane junctions.

2. **Orai1, Orai2, and Orai3:** These proteins form the pore-forming subunits of SOCs and are located in the plasma membrane. Upon STIM1/STIM2 activation, they interact with the STIM proteins, forming a complex that allows for calcium influx.

3. **CRACM1 (Calcium release-activated calcium modulator 1):** This protein acts as a regulatory subunit of the SOC channel complex. While not directly involved in calcium influx, CRACM1 is crucial for proper channel function and stability.

The activation process unfolds as follows:

1. **Depletion of ER calcium:** Various stimuli, such as receptor activation, depletion of ATP, or changes in membrane potential, can lead to the release of calcium from the ER.

2. **STIM1/STIM2 activation:** ER calcium depletion causes STIM1 and STIM2 to sense the decreased calcium levels within the ER lumen. This triggers conformational changes in the proteins, resulting in their oligomerization and their movement towards ER-plasma membrane junctions.

3. **STIM1/STIM2-Orai interaction:** At these junctions, STIM1 and STIM2 interact with the Orai proteins, which are located in the plasma membrane. This interaction leads to the formation of a functional SOC channel complex.

4. **Calcium influx:** The formation of the complex allows for calcium to flow from the extracellular space into the cytoplasm through the Orai pore. This influx of calcium replenishes the depleted ER stores and restores calcium homeostasis.

5. **Feedback regulation:** The calcium influx through SOCs triggers negative feedback mechanisms that limit the channel's activity. These mechanisms include:
* **Calcium-dependent inactivation:** High intracellular calcium levels can directly inhibit SOC channel activity.
* **STIM1/STIM2 dephosphorylation:** The phosphorylation state of STIM1 and STIM2 influences their interaction with Orai, affecting channel activation.

Overall, the activation of SOCs is a tightly regulated process that involves a complex interplay of proteins and signaling pathways. This intricate mechanism ensures that calcium influx occurs only when needed, preventing uncontrolled calcium signaling and maintaining cellular homeostasis.'"

Proteins (2)

Compounds (4)