Related Experiment Video
Updated: May 22, 2026

Isolation of Peritoneum-derived Mast Cells and Their Functional Characterization with Ca2+-imaging and Degranulation Assays
Published on: July 4, 2018
Roles for ca(2+) mobilization and its regulation in mast cell functions
David Holowka1, Nathaniel Calloway, Roy Cohen
1Department of Chemistry and Chemical Biology, Cornell University Ithaca, NY, USA.
Insights
Calcium mobilization is crucial for mast cell function, driven by IgE receptor signaling. STIM1 and Orai1 proteins regulate calcium influx, impacting exocytosis and cell migration.
Area of Science:
- Immunology
- Cellular Biology
- Molecular Biology
Background:
- Mast cells play a critical role in allergic responses and immunity.
- Immunoglobulin E (IgE) receptor signaling is central to mast cell activation.
- Calcium (Ca2+) mobilization is a key downstream event in IgE receptor-mediated mast cell activation.
Purpose of the Study:
- To summarize the molecular mechanisms of Ca2+ mobilization in mast cells.
- To elucidate the physiological roles of Ca2+ signaling in mast cell functions.
- To highlight the involvement of phosphoinositide metabolism in these processes.
Main Methods:
- Review of existing literature on IgE receptor signaling and Ca2+ dynamics.
- Focus on the STIM1-Orai1 coupling mechanism for Ca2+ influx.
- Analysis of Ca2+ roles in granule exocytosis, endosome trafficking, cytokine release, and chemotaxis.
Main Results:
- IgE receptor activation triggers rapid Ca2+ waves and oscillations.
- STIM1 and Orai1 mediate Ca2+ influx essential for sustained signaling.
- Ca2+ mobilization is vital for mast cell degranulation, cytokine secretion, and migration.
Conclusions:
- Ca2+ mobilization is a fundamental process governing multiple mast cell functions.
- The STIM1-Orai1 pathway is a critical regulator of antigen-induced Ca2+ signaling.
- Understanding these pathways offers insights into mast cell-related diseases and potential therapeutic targets.
Abstract:
Mobilization of Ca(2+) in response to IgE receptor-mediated signaling is a key process in many aspects of mast cell function. Here we summarize our current understanding of the molecular bases for this process and the roles that it plays in physiologically relevant mast cell biology. Activation of IgE receptor signaling by antigen that crosslinks these complexes initiates Ca(2+) mobilization as a fast wave that is frequently followed by a series of Ca(2+) oscillations which are dependent on Ca(2+) influx-mediated by coupling of the endoplasmic reticulum luminal Ca(2+) sensor STIM1 to the calcium release activated calcium channel protein Orai1. Granule exocytosis depends on this process, together with the activation of protein kinase C isoforms, and specific roles for these signaling steps are beginning to be understood. Ca(2+) mobilization also plays important roles in stimulated exocytosis of recycling endosomes and newly synthesized cytokines, as well as in antigen-mediated chemotaxis of rat mucosal mast cells. Phosphoinositide metabolism plays key roles in all of these processes, and we highlight these roles in several cases.
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...
Amplifying Signals via Second Messengers
IP3/DAG Signaling Pathway
Cell Polarization by Rho Proteins
GPCRs Regulate Adenylyl Cylase Activity
Two...

