Related Experiment Video
Updated: Mar 17, 2026

Visualizing the Actin and Microtubule Cytoskeletons at the B-cell Immune Synapse Using Stimulated Emission Depletion STED Microscopy
Published on: April 9, 2018
Calcium influx through CRAC channels controls actin organization and dynamics at the immune synapse
Catherine A Hartzell1,2, Katarzyna I Jankowska3,4, Janis K Burkhardt3,4
1Immunology Program, Stanford University, Stanford, United States.
Insights
Calcium influx is essential for organizing actin dynamics at the immune synapse. This process regulates T cell receptor signaling intensity and duration by controlling actin polymerization and retrograde flow.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- T cell receptor (TCR) engagement initiates calcium (Ca2+) influx via CRAC channels, forming an immune synapse.
- Actin reorganization and retrograde flow at the synapse regulate TCR signaling duration and intensity.
Purpose of the Study:
- To investigate the role of Ca2+ influx in regulating actin organization and dynamics at the immune synapse.
- To elucidate the mechanisms by which Ca2+ influences actin polymerization, depolymerization, and retrograde flow.
Main Methods:
- Live-cell imaging of actin dynamics and Ca2+ signaling at the immune synapse.
- Perturbation of Ca2+ influx and analysis of downstream effects on actin.
Main Results:
- Ca2+ influx is required for proper actin organization and dynamics at the immune synapse.
- Calcium promotes actin depolymerization and directs WAVE2 localization to the lamellipod periphery.
- Ca2+-dependent retrograde actin flow corrals ER tubules and STIM1/Orai1 complexes to the synapse center.
Conclusions:
- Ca2+ acts as a critical regulator of actin organization and dynamics at the immune synapse.
- This Ca2+-mediated regulation of actin may involve feedback loops modulating TCR signaling.
Abstract:
T cell receptor (TCR) engagement opens Ca(2+) release-activated Ca(2+) (CRAC) channels and triggers formation of an immune synapse between T cells and antigen-presenting cells. At the synapse, actin reorganizes into a concentric lamellipod and lamella with retrograde actin flow that helps regulate the intensity and duration of TCR signaling. We find that Ca(2+) influx is required to drive actin organization and dynamics at the synapse. Calcium acts by promoting actin depolymerization and localizing actin polymerization and the actin nucleation promotion factor WAVE2 to the periphery of the lamellipod while suppressing polymerization elsewhere. Ca(2+)-dependent retrograde actin flow corrals ER tubule extensions and STIM1/Orai1 complexes to the synapse center, creating a self-organizing process for CRAC channel localization. Our results demonstrate a new role for Ca(2+) as a critical regulator of actin organization and dynamics at the synapse, and reveal potential feedback loops through which Ca(2+) influx may modulate TCR signaling.
Related Concept Videos
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...
Intracellular Signaling Affects Focal Adhesions
Some...
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,...
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Relaxation of Skeletal Muscles
When an action potential reaches the axon terminal, it depolarizes the membrane and opens voltage-gated sodium channels. Sodium ions enter the cell, further depolarizing the presynaptic membrane. This depolarization causes voltage-gated calcium channels to open....
Formation of Higher-order Actin Filaments
The high-order actin...

