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Critical parameters maintaining authentic CRAC channel hallmarks.

Adéla Krizova1, Lena Maltan1, Isabella Derler2

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European Biophysics Journal : EBJ
|March 24, 2019
PubMed
Summary
This summary is machine-generated.

Calcium ions (Ca2+) are vital cell messengers. This review details how STIM1 and Orai proteins form CRAC channels, crucial for Ca2+ entry, and their key structural and functional characteristics.

Keywords:
CRAC channelCalciumElectrophysiologyFRETGain-of-function mutantsOrai gatingOrai1STIM1STIM–Orai interactionStructural resolution

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Area of Science:

  • Cell Biology
  • Ion Channel Physiology
  • Molecular Biophysics

Background:

  • Calcium ions (Ca2+) act as essential second messengers regulating diverse cellular processes.
  • The Ca2+ release-activated Ca2+ (CRAC) channel is a primary pathway for Ca2+ entry into cells.
  • CRAC channels are formed by the interaction of stromal interaction molecule 1 (STIM1) and Orai proteins.

Purpose of the Study:

  • To review the critical determinants and structures within STIM1 and Orai proteins.
  • To elucidate the molecular mechanisms underlying CRAC channel characteristics.
  • To provide an overview of the biophysical properties of CRAC channels.

Main Methods:

  • Literature review of studies on STIM1 and Orai proteins.
  • Analysis of structural and biophysical data related to CRAC channel function.
  • Synthesis of information on Ca2+ signaling and ion channel regulation.

Main Results:

  • STIM1, a Ca2+ sensor in the endoplasmic reticulum, activates Orai channels in the plasma membrane upon Ca2+ store depletion.
  • CRAC channels exhibit high Ca2+ selectivity, a reversal potential around +50 mV, small unitary conductance, and fast Ca2+-dependent inactivation.
  • Currents through CRAC channels are enhanced when switching from a Na+-containing divalent-free solution to a Ca2+-containing solution.

Conclusions:

  • The interplay between STIM1 and Orai is fundamental for establishing the unique biophysical properties of CRAC channels.
  • Understanding the structural determinants of STIM1 and Orai is key to comprehending CRAC channel function.
  • This review consolidates current knowledge on the molecular basis of CRAC channel activity and its physiological relevance.