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Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

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Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
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Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
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Feedback Regulation of Calcium Concentration01:27

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Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
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Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
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Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
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Because many receptor binding ligands are hydrophilic, they do not cross the cell membrane and thus their message must be relayed to a second messenger on the inside. There are several second messenger pathways, each with their own way of relaying information. G-protein coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol path is active when the receptor induces phospholipase C to hydrolyze the phospholipid,...
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NAADP-induced Ca2+ release -- a new signalling pathway.

Sandip Patel1

  • 1Department of Physiology, University College London, London, United Kingdom. patel.s@ucl.ac.uk

Biology of the Cell
|April 20, 2004
PubMed
Summary

Nicotinic acid adenine dinucleotide phosphate (NAADP) regulates cellular calcium. This new messenger targets a unique calcium channel, distinct from the endoplasmic reticulum, influencing cellular signaling pathways.

Area of Science:

  • Cellular Biology
  • Molecular Physiology
  • Biochemistry

Background:

  • Cytosolic calcium (Ca2+) concentration is vital for regulating cellular functions.
  • Calcium mobilization from intracellular stores via calcium-mobilizing messengers is a conserved mechanism.
  • Nicotinic acid adenine dinucleotide phosphate (NAADP) is a recently identified calcium-mobilizing messenger.

Purpose of the Study:

  • To investigate the role and mechanism of NAADP in cellular calcium regulation.
  • To identify the specific intracellular calcium release channel targeted by NAADP.
  • To understand the implications of NAADP signaling in cellular dynamics.

Main Methods:

  • Literature review and synthesis of existing research on NAADP.
  • Analysis of experimental data demonstrating NAADP's interaction with calcium channels.

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  • Investigation of calcium dynamics and cross-talk between different intracellular calcium channels.

    • Main Results:

    • NAADP targets a novel intracellular calcium release channel, potentially distinct from the endoplasmic reticulum.
    • This NAADP-sensitive channel may exhibit inactivation before opening under specific conditions.
    • Physiologically relevant stimuli have been shown to alter cellular NAADP levels, impacting calcium dynamics.

    Conclusions:

    • NAADP plays a significant role in controlling cellular calcium homeostasis.
    • The novel NAADP-sensitive channel contributes to complex calcium signaling events.
    • Understanding NAADP pathways is crucial for comprehending cellular communication and function.