Related Experiment Video
Updated: Jul 4, 2026

Whole-Cell Recording of Calcium Release-Activated Calcium (CRAC) Currents in Human T Lymphocytes
Published on: December 21, 2010
Calcium signaling in lymphocytes
Masatsugu Oh-hora1, Anjana Rao
1Department of Pathology, Harvard Medical School, Immune Disease Institute, Boston, MA 02115, USA.
Insights
Calcium signals are vital for immune cell functions. This review details the STIM/ORAI and calcineurin/NFAT pathways regulating store-operated calcium entry via CRAC channels.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Calcium signals are crucial for immune cell functions like differentiation and gene transcription.
- Immunoreceptor engagement triggers intracellular calcium increases via store depletion and subsequent entry.
- Store-operated calcium entry through CRAC channels is a major pathway for calcium increase in immune cells.
Purpose of the Study:
- To review the signaling pathways upstream and downstream of calcium influx.
- To highlight the roles of STIM and ORAI in regulating CRAC channel function.
- To provide insights into the molecular mechanisms of calcium signaling in immune cells.
Main Methods:
- Literature review of recent breakthroughs in CRAC channel research.
- Focus on signaling pathways involving STIM, ORAI, calcineurin, and NFAT.
- Analysis of the sequential operation of calcium store depletion and entry.
Main Results:
- Identification of STIM and ORAI as key regulators of CRAC channels.
- Elucidation of the STIM/ORAI pathway upstream of calcium influx.
- Description of the calcineurin/NFAT pathway downstream of calcium influx.
Conclusions:
- STIM and ORAI are essential for store-operated calcium entry in immune cells.
- Understanding these pathways is critical for comprehending immune cell function.
- This review consolidates current knowledge on CRAC channel regulation and downstream signaling.
Abstract:
In cells of the immune system, calcium signals are essential for diverse cellular functions including differentiation, effector function, and gene transcription. After the engagement of immunoreceptors such as T-cell and B-cell antigen receptors and the Fc receptors on mast cells and NK cells, the intracellular concentration of calcium ions is increased through the sequential operation of two interdependent processes: depletion of endoplasmic reticulum Ca(2+) stores as a result of binding of inositol trisphosphate (IP(3)) to IP(3) receptors, followed by 'store-operated' Ca(2+) entry through plasma membrane Ca(2+) channels. In lymphocytes, mast cells and other immune cell types, store-operated Ca(2+) entry through specialized Ca(2+) release-activated calcium (CRAC) channels constitutes the major pathway of intracellular Ca(2+) increase. A recent breakthrough in our understanding of CRAC channel function is the identification of stromal interaction molecule (STIM) and ORAI, two essential regulators of CRAC channel function. This review focuses on the signaling pathways upstream and downstream of Ca(2+) influx (the STIM/ORAI and calcineurin/NFAT pathways, respectively).
Related Concept Videos
Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Feedback Regulation of Calcium Concentration
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
B Cell Activation and Differentiation
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
Amplifying Signals via Second Messengers
Lymphoid Cells and Tissues
Lymphoid cells consist of various types of immune system cells. These include B and T lymphocytes, which are responsible for producing antibodies and killing infected cells, respectively. Dendritic cells act as messengers between the innate and adaptive...
The JAK-STAT Signaling Pathway

