release of sequestered calcium ion into cytosol by endoplasmic reticulum

Definition

Target type: biologicalprocess

The directed movement of calcium ion from endoplasmic reticulum to cytosol. [GO_REF:0000078, GOC:BHF, GOC:mtg_cardiac_conduct_nov11, GOC:rl, GOC:TermGenie, PMID:16402920]

The release of sequestered calcium ions from the endoplasmic reticulum (ER) into the cytosol is a critical signaling event in eukaryotic cells. This process is tightly regulated and involves a complex interplay of proteins and signaling molecules.

The ER serves as the primary intracellular calcium store, maintaining a high concentration of Ca2+ within its lumen. This calcium gradient is established and maintained by active transport systems, such as the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump, which uses ATP to pump Ca2+ from the cytosol into the ER lumen.

The release of calcium from the ER is triggered by a variety of stimuli, including:

- **Ligand binding to G protein-coupled receptors (GPCRs):** This activation leads to the production of inositol triphosphate (IP3), a second messenger that binds to IP3 receptors (IP3Rs) located on the ER membrane.

- **Depolarization of the plasma membrane:** This can occur in response to electrical signals or neurotransmitters, leading to the opening of voltage-gated calcium channels (VGCCs) on the plasma membrane. The influx of Ca2+ from the extracellular space can then activate calcium-induced calcium release (CICR) mechanisms, triggering the release of Ca2+ from the ER.

- **Mechanical stimuli:** Mechanical stress or deformation of the cell can trigger the release of calcium from the ER. This can involve physical interactions between the ER and other cellular structures or the activation of mechanosensitive channels.

The release of Ca2+ from the ER is mediated by specific calcium channels:

- **IP3 receptors (IP3Rs):** These channels are activated by IP3 and allow Ca2+ to flow from the ER lumen into the cytosol. They are tetramers, with each subunit containing a binding site for IP3 and a Ca2+ channel pore.

- **Ryanodine receptors (RyRs):** These channels are activated by a combination of factors, including Ca2+ itself (CICR), and play a critical role in muscle contraction and other cellular processes. They are also tetramers and share structural similarity with IP3Rs.

Once released into the cytosol, calcium ions activate a wide range of cellular signaling pathways. These include:

- **Muscle contraction:** In muscle cells, Ca2+ binds to troponin, a protein associated with the actin filaments, triggering muscle contraction.

- **Exocytosis:** Ca2+ plays a crucial role in the release of neurotransmitters and hormones from cells.

- **Gene expression:** Ca2+ signaling can regulate gene expression by activating specific transcription factors.

- **Cell growth and differentiation:** Ca2+ plays a role in cell cycle progression and differentiation.

- **Apoptosis:** Ca2+ signaling can trigger apoptosis, a form of programmed cell death.

The release of Ca2+ from the ER is a tightly controlled process, and its dysregulation can lead to various diseases. For example, mutations in IP3Rs or RyRs have been linked to neurological disorders, while disruptions in calcium signaling can contribute to cardiovascular diseases and cancer.

The specific mechanisms and pathways involved in Ca2+ release from the ER vary depending on the cell type and the specific stimulus. However, the basic principles of calcium signaling remain conserved across eukaryotic cells.'
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