Related Experiment Video

Updated: May 21, 2025

Studying Interactions of Staphylococcus aureus with Neutrophils by Flow Cytometry and Time Lapse Microscopy
10:40

Studying Interactions of Staphylococcus aureus with Neutrophils by Flow Cytometry and Time Lapse Microscopy

Published on: July 17, 2013

13.0K

STIM1/2 maintain signaling competence at ER-PM contact sites during neutrophil spreading

Camille Rabesahala de Meritens1, Amado Carreras-Sureda1, Nicolas Rosa1

  • 1Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.

The Journal of Cell Biology
|March 21, 2025
PubMed

Insights

Stim proteins (Stim1/2) are crucial for neutrophil calcium (Ca2+) signaling, controlling actin dynamics and cell spreading. Their absence impairs neutrophil migration and actin formation, highlighting their role in immune cell motility.

Area of Science:

  • Immunology
  • Cell Biology
  • Calcium Signaling

Background:

  • Neutrophils are key immune cells for pathogen destruction.
  • Calcium (Ca2+) signals regulate leukocyte migration.
  • The role of Stim proteins in neutrophil motility and actin dynamics was unclear.

Purpose of the Study:

  • To investigate the role of Stim1 and Stim2 proteins in neutrophil calcium (Ca2+) fluxes.
  • To determine how Stim proteins regulate neutrophil actin-based motility and spreading.
  • To elucidate the mechanism by which Stim proteins influence calcium signaling at ER-PM contact sites.

Main Methods:

  • Myeloid-specific Stim1/2 ablation in mouse neutrophils.
  • Measurement of cytosolic Ca2+ levels and adhesion-induced Ca2+ elevations.
  • Analysis of actin fiber formation and neutrophil spreading.
  • Confocal and immunogold microscopy to assess ER-PM contact sites and IP3R localization.
  • In vivo recruitment assays in mouse inflamed cremaster muscles.

Main Results:

  • Stim1/2 deficiency reduced basal and adhesion-induced Ca2+ levels, impairing neutrophil spreading and actin formation.
  • Stim1/2-deficient neutrophils showed increased ER-PM contact sites but reduced inositol-1,4,5-trisphosphate receptor (IP3R) immunoreactivity.
  • Restoring Ca2+-rich conditions or in vivo inflammation improved Stim1/2-deficient neutrophil function and recruitment.
  • Stim1/2 proteins are essential for maintaining IP3R functionality at adhesive membranes.

Conclusions:

  • Stim1/2 proteins are critical for adhesion-dependent Ca2+ signals that regulate neutrophil actin dynamics and spreading.
  • Stim proteins ensure IP3R signaling competence, enabling Ca2+-dependent actin remodeling in neutrophils.
  • Targeting Stim proteins could offer new strategies for modulating neutrophil function in inflammatory diseases.

More Related Videos

Measuring Cell-Edge Protrusion Dynamics during Spreading using Live-Cell Microscopy05:50

Measuring Cell-Edge Protrusion Dynamics during Spreading using Live-Cell Microscopy

Published on: November 1, 2021

2.3K
Analyzing the Effects of Stromal Cells on the Recruitment of Leukocytes from Flow11:30

Analyzing the Effects of Stromal Cells on the Recruitment of Leukocytes from Flow

Published on: January 7, 2015

10.2K

Related Concept Videos

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
2.5K
Adherens Junctions01:24

Adherens Junctions

Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types –  adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as  epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as  heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
Adherens Junctions are Dynamic
4.6K
Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
3.2K
Selectins01:25

Selectins

Cell adhesion is  an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain,...
3.2K
Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.3K