calcium-induced calcium release activity

Definition

Target type: molecularfunction

Enables transmembrane transfer of calcium ions from an intracellular store to the cytosol on induction by increased calcium concentration. [GOC:jid, GOC:nln, PMID:2990997, PMID:8381210, PMID:8653752]

Calcium-induced calcium release (CICR) is a fundamental process in cellular signaling that amplifies calcium signals and plays a crucial role in various physiological processes. It involves the release of calcium ions (Ca2+) from intracellular stores, primarily the endoplasmic reticulum (ER) or sarcoplasmic reticulum (SR), triggered by an initial rise in cytosolic Ca2+ concentration. This positive feedback mechanism allows for rapid and localized increases in intracellular Ca2+ concentration, triggering downstream cellular responses.

The molecular mechanism of CICR involves the interplay of specialized Ca2+ channels in the ER/SR membrane, specifically the ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs). These channels are responsible for mediating Ca2+ release from the intracellular stores.

RyRs are primarily found in muscle cells and are activated by a rise in cytosolic Ca2+ concentration. They form large, tetrameric protein complexes that act as Ca2+-gated Ca2+ channels. When cytosolic Ca2+ levels increase, RyRs open, allowing Ca2+ to flow from the SR into the cytosol. This influx of Ca2+ further enhances the Ca2+ signal, creating a positive feedback loop.

IP3Rs are located in various cell types and are activated by both Ca2+ and inositol 1,4,5-trisphosphate (IP3), a second messenger produced by the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2). Similar to RyRs, IP3Rs are Ca2+-gated Ca2+ channels that open when cytosolic Ca2+ levels rise. However, IP3Rs can also be activated by IP3, which binds to the receptor and triggers channel opening.

The regulation of CICR is tightly controlled by a complex network of proteins and signaling pathways. Various factors, including the concentration of Ca2+ in the cytosol and intracellular stores, the availability of IP3, and the activity of protein kinases and phosphatases, contribute to the fine-tuning of Ca2+ release.

CICR plays a vital role in numerous physiological processes, including:

* Muscle contraction: CICR is essential for the excitation-contraction coupling in muscle cells. It ensures rapid and synchronized release of Ca2+ from the SR, triggering muscle fiber contraction.
* Neuronal signaling: CICR contributes to synaptic transmission by facilitating the release of neurotransmitters from presynaptic terminals.
* Hormone secretion: CICR plays a role in regulating hormone release from endocrine cells, such as pancreatic beta cells releasing insulin.
* Cell growth and differentiation: CICR is involved in regulating cell proliferation, differentiation, and apoptosis.
* Immune response: CICR participates in immune cell activation and signaling, contributing to the inflammatory response.

Disruptions in CICR can lead to various pathological conditions, including:

* Muscle diseases: Mutations in RyRs can cause muscle weakness, fatigue, and cramps.
* Cardiac arrhythmias: Dysregulation of CICR in the heart can contribute to abnormal heart rhythms and heart failure.
* Neurological disorders: Abnormalities in CICR may contribute to epilepsy, Alzheimer's disease, and Parkinson's disease.
* Cancer: Altered CICR signaling can promote cancer cell growth and metastasis.

In summary, CICR is a complex and critical process in cellular signaling that amplifies calcium signals and plays a pivotal role in numerous physiological functions. Its regulation and proper functioning are crucial for maintaining cellular homeostasis and preventing disease.'
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Proteins (2)

Compounds (4)