store-operated calcium entry

Definition

Target type: biologicalprocess

A calcium ion entry mechanism in the plasma membrane activated by the depletion of calcium ion from the internal calcium ion store in the endoplasmic reticulum. [GOC:hjd, PMID:11120592, PMID:17956991]

Store-operated calcium entry (SOCE) is a fundamental cellular process responsible for maintaining calcium homeostasis and regulating diverse cellular functions. It involves the replenishment of intracellular calcium stores, primarily the endoplasmic reticulum (ER), through the influx of extracellular calcium. SOCE is triggered by the depletion of calcium from the ER, which activates a signaling cascade leading to the opening of plasma membrane calcium channels known as Orai1 channels. Here is a detailed description of the process:

1. **ER Calcium Depletion:** The ER serves as the primary intracellular calcium store. When intracellular calcium levels are low, the ER releases its calcium content through various mechanisms, including IP3 receptor activation, ryanodine receptor activation, and other calcium-releasing channels. This depletion of ER calcium triggers the activation of SOCE.

2. **STIM1 Sensing and Activation:** STIM1 is a transmembrane protein located in the ER membrane. It acts as the primary sensor of ER calcium depletion. Upon sensing the drop in ER calcium, STIM1 undergoes a conformational change and oligomerizes, forming clusters within the ER membrane.

3. **STIM1-Orai1 Interaction and Channel Activation:** Activated STIM1 interacts with Orai1 channels, which are plasma membrane calcium channels. The interaction between STIM1 and Orai1 is essential for the activation and opening of Orai1 channels. This interaction is mediated by the coiled-coil domain of STIM1 and the cytosolic domain of Orai1.

4. **Calcium Influx:** Once the Orai1 channels are activated, they open, allowing calcium ions from the extracellular space to enter the cell. The influx of calcium through Orai1 channels replenishes the depleted ER calcium stores and restores calcium homeostasis.

5. **Regulation of SOCE:** SOCE is tightly regulated by a complex interplay of factors, including:
- **Calcium Feedback Mechanism:** Increased intracellular calcium levels can feedback to inhibit further calcium entry through Orai1 channels.
- **Phosphatases and Kinases:** Various phosphatases and kinases can modulate the activity of STIM1 and Orai1, fine-tuning SOCE.
- **Other Cellular Signaling Pathways:** SOCE can be influenced by other signaling pathways, such as those involving Ras, Rho, and Src kinases.

6. **Cellular Functions Regulated by SOCE:** SOCE plays a critical role in a wide range of cellular functions, including:
- **Muscle Contraction:** In muscle cells, SOCE contributes to the release of calcium from the sarcoplasmic reticulum, triggering muscle contraction.
- **Exocytosis:** SOCE is involved in the regulated secretion of hormones, neurotransmitters, and other cellular products.
- **Gene Expression:** Calcium influx through SOCE can activate transcription factors and regulate gene expression.
- **Cell Growth and Differentiation:** SOCE is essential for cell proliferation, differentiation, and migration.
- **Immune Responses:** SOCE plays a crucial role in immune cell activation, such as T cell activation and mast cell degranulation.

In summary, SOCE is a complex and essential cellular process that ensures the replenishment of intracellular calcium stores and regulates diverse cellular functions. The intricate interaction between STIM1 and Orai1 proteins, along with its regulation by various cellular signaling pathways, underlines the importance of SOCE in maintaining cellular homeostasis and mediating critical cellular events.'
"

Proteins (5)

Compounds (12)