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Related Concept Videos

Feedback Regulation of Calcium Concentration01:27

Feedback Regulation of Calcium Concentration

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.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

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.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
Mechanically-gated Ion Channels01:12

Mechanically-gated Ion Channels

Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
Mechanically-gated Ion Channels01:12

Mechanically-gated Ion Channels

Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
Non-gated Ion Channels01:24

Non-gated Ion Channels

Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.

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Fluorescence-based Measurement of Store-operated Calcium Entry in Live Cells: from Cultured Cancer Cell to Skeletal Muscle Fiber
14:18

Fluorescence-based Measurement of Store-operated Calcium Entry in Live Cells: from Cultured Cancer Cell to Skeletal Muscle Fiber

Published on: February 13, 2012

STIMulating store-operated Ca(2+) entry.

Michael D Cahalan1

  • 1Department of Physiology and Biophysics and Institute for Immunology, University of California, Irvine, CA 92697-4561, USA. mcahalan@uci.edu

Nature Cell Biology
|June 3, 2009
PubMed
Summary
This summary is machine-generated.

Store-operated calcium (SOC) channels regulate cellular calcium levels. STIM1 was identified as the key protein linking endoplasmic reticulum calcium depletion to SOC channel activation, explaining this vital signaling mechanism.

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Area of Science:

  • Cell Biology
  • Molecular Physiology
  • Calcium Signaling

Background:

  • Store-operated calcium (SOC) channels mediate calcium influx in response to endoplasmic reticulum (ER) calcium depletion.
  • This homeostatic calcium signaling mechanism was poorly understood for over 20 years.
  • Identifying the molecular components linking ER calcium stores to plasma membrane channels was a critical research gap.

Purpose of the Study:

  • To elucidate the molecular mechanism underlying store-operated calcium entry.
  • To identify the protein(s) responsible for sensing ER calcium levels and gating plasma membrane channels.

Main Methods:

  • RNA-interference (RNAi) screening was employed to identify key regulatory proteins.
  • Molecular and cellular physiological analyses were conducted to validate findings.
  • Investigated the role of STIM1 in the context of ER calcium depletion and SOC channel activity.

Main Results:

  • STIM1 was identified as the crucial 'missing link' between the ER and plasma membrane.
  • STIM1 senses ER calcium store depletion, leading to its oligomerization and translocation.
  • STIM1 organizes and activates Orai or TRPC channels, facilitating SOC entry.

Conclusions:

  • STIM1 is the essential sensor and activator of store-operated calcium channels.
  • This discovery provides a mechanistic explanation for a fundamental calcium signaling pathway.
  • Understanding STIM1's role is key to comprehending cellular calcium homeostasis and related pathologies.