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.

Related Concept Videos

Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
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 Concentration01:27

Feedback Regulation of Calcium Concentration

Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
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 Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
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 Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
Lymphoid Cells and Tissues01:18

Lymphoid Cells and Tissues

Lymphoid cells and tissues are integral to the immune system, which is crucial in maintaining our body's defense against harmful pathogens. They form the building blocks of lymphoid organs, which include the spleen, thymus, and lymph nodes.
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 Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...