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Whole-Cell Recording of Calcium Release-Activated Calcium (CRAC) Currents in Human T Lymphocytes
15:29

Whole-Cell Recording of Calcium Release-Activated Calcium (CRAC) Currents in Human T Lymphocytes

Published on: December 21, 2010

A novel EF-hand protein, CRACR2A, is a cytosolic Ca2+ sensor that stabilizes CRAC channels in T cells

Sonal Srikanth1, Hea-Jin Jung, Kyun-Do Kim

  • 1Department of Physiology, David Geffen School of Medicine at the University of California, Los Angeles, California 90095, USA.

Nature Cell Biology
|April 27, 2010
PubMed

Insights

A novel calcium-binding protein, CRACR2A, regulates calcium release-activated calcium (CRAC) channels by interacting with Orai1 and STIM1. This protein is crucial for store-operated calcium entry (SOCE) in immune cells, particularly T cells.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Orai1 and STIM1 are essential for calcium release-activated calcium (CRAC) channels, mediating store-operated calcium entry (SOCE) in immune cells.
  • The cytoplasmic machinery controlling Orai1 and STIM1 clustering and function in SOCE is not fully understood.

Purpose of the Study:

  • To identify novel modulators of Orai1 and STIM1 function in CRAC channel activity.
  • To elucidate the role of newly identified proteins in the regulation of store-operated calcium entry.

Main Methods:

  • Affinity protein purification was used to identify proteins interacting with Orai1 and STIM1.
  • Small interfering RNA (siRNA) mediated knockdown and mutagenesis were employed to study protein function.
  • Cellular assays were performed to assess calcium levels and protein clustering.

Main Results:

  • A novel EF-hand protein, CRACR2A, was identified as a direct interactor of Orai1 and STIM1, forming a ternary complex.
  • CRACR2A is essential for the clustering of Orai1 and STIM1 upon calcium store depletion.
  • An EF-hand mutant of CRACR2A promoted STIM1 clustering, increased cytoplasmic calcium, and induced cell death.

Conclusions:

  • CRACR2A is a novel calcium-binding protein that plays a critical role in regulating CRAC channel-mediated SOCE.
  • CRACR2A is highly expressed in T cells and conserved across vertebrates, highlighting its importance in immune cell function.

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