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Monitoring Leucine-Rich Repeat Containing 8 Channel (LRRC8/VRAC) Activity Using Sensitized-Emission Förster Resonance Energy Transfer (SE-FRET)
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The molecular physiology of CRAC channels

Murali Prakriya1

  • 1Department of Molecular Pharmacology and Biological Chemistry, Northwestern University School of Medicine, Chicago, IL 60611, USA. m-prakriya@northwestern.edu

Immunological Reviews
|September 17, 2009
PubMed

Insights

Calcium release-activated calcium (CRAC) channels, crucial for cellular functions, are regulated by STIM1 and Orai1 proteins. Recent studies reveal their activation mechanisms, pore properties, and high calcium selectivity.

Area of Science:

  • Cell Biology
  • Ion Channel Physiology
  • Immunology

Background:

  • Calcium release-activated calcium (CRAC) channels are essential store-operated channels regulating cellular processes in immune and other cells.
  • CRAC channels are critical for gene expression, cell motility, and inflammatory mediator secretion.
  • Orai1 and STIM1 proteins are key components of the CRAC channel complex, involved in its regulation and function.

Purpose of the Study:

  • To review recent advancements in understanding CRAC channel activation mechanisms.
  • To elucidate the pore properties and selectivity of CRAC channels.
  • To summarize the modulation and regulation of CRAC channel activity.

Main Methods:

  • Literature review of recent studies on CRAC channel function.
  • Analysis of structure-function studies identifying protein interactions and pore domains.
  • Examination of evidence detailing STIM1 and Orai1 redistribution and conformational changes.

Main Results:

  • CRAC channel activation involves coordinated STIM1 and Orai1 redistribution, interaction, and Orai1 conformational changes upon store depletion.
  • High Ca2+ selectivity is attributed to an intrapore Ca2+ binding site that prevents Na+ permeation.
  • Structure-function studies have identified potential Ca2+ binding sites within the CRAC channel pore.

Conclusions:

  • Recent progress has significantly advanced the understanding of CRAC channel activation and gating mechanisms.
  • The precise pore structure and intrapore binding sites are key to the channel's high Ca2+ selectivity.
  • Further research provides a framework for understanding CRAC channel function and potential therapeutic modulation.

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