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Related Concept Videos

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...
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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

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Ion Channels01:19

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The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
Ion channels are specialized integral membrane proteins on the plasma membrane that allow specific...
Non-gated Ion Channels01:24

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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.
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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Monitoring Leucine-Rich Repeat Containing 8 Channel (LRRC8/VRAC) Activity Using Sensitized-Emission F&#246;rster Resonance Energy Transfer (SE-FRET)
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Store-operated Orai channels: structure and function.

Murali Prakriya1

  • 1Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA. m-prakriya@northwestern.edu

Current Topics in Membranes
|July 30, 2013
PubMed
Summary

Store-operated calcium (Ca2+) release-activated Ca2+ (CRAC) channels are vital for cell function and disease. STIM1 and Orai1 proteins mediate CRAC channel activation following calcium store depletion.

Keywords:
CRAC channelGatingOrai1PermeationReviewSTIM1Store-operated channel

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Area of Science:

  • Cellular Biology
  • Molecular Physiology

Background:

  • Store-operated calcium (Ca2+) release-activated Ca2+ (CRAC) channels are critical for numerous cellular processes, including gene expression, motility, and proliferation.
  • Dysfunction of CRAC channels is implicated in diseases such as severe combined immunodeficiency syndrome, highlighting their therapeutic potential.
  • Decades of research have elucidated the fundamental roles of CRAC channels, yet their precise molecular mechanisms remained elusive until recent discoveries.

Purpose of the Study:

  • To review the molecular mechanisms governing the operation and function of CRAC channels.
  • To highlight the roles of STIM1 and Orai1 proteins in CRAC channel regulation.
  • To discuss the structural features of STIM and Orai proteins that control CRAC channel gating and ion conduction.

Main Methods:

  • Review of existing literature on CRAC channel function and molecular mechanisms.
  • Focus on the discovery and characterization of Orai1 and STIM1 proteins.
  • Analysis of protein-protein interactions and cellular redistribution events.

Main Results:

  • The discovery of Orai1 and STIM1 has significantly advanced the understanding of CRAC channel operation.
  • CRAC channel activation involves the redistribution of STIM1 and Orai1 to peripheral sites upon endoplasmic reticulum (ER) Ca2+ store depletion.
  • Direct protein-protein interactions between STIM1 and Orai1 are essential for CRAC channel gating.

Conclusions:

  • STIM1 and Orai1 are key regulators of CRAC channel activity.
  • Understanding the molecular interplay between STIM1 and Orai1 provides insights into CRAC channel function and disease.
  • Further investigation into the molecular features of STIM and Orai proteins can inform drug development for CRAC channel-related disorders.