Related Experiment Video
Updated: Jul 8, 2025
04:15
Author Spotlight: Development of a Method for Identifying Small Molecular Antagonists of β2 Integrin Activation
Published on: February 2, 2024
1.8K
The Rac-GEF Tiam1 controls integrin-dependent neutrophil responses.
Kirsti Hornigold1, Martin J Baker1,2, Polly A Machin1
1Signalling Programme, Babraham Institute, Cambridge, United Kingdom.
Frontiers in Immunology
|December 11, 2023
Summary
Tiam1 regulates neutrophil responses, controlling actin dynamics and migration differently than other Rac-GEFs. It restricts adhesion and Rac activation, impacting bacterial killing and immune cell recruitment.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Rac GTPases are crucial for neutrophil functions like adhesion, migration, and pathogen killing.
- Neutrophil Rac-GEFs from Prex, Vav, and Dock families activate Rac GTPases.
- The role of Tiam1, another Rac-GEF, in neutrophils remained largely unexplored.
Purpose of the Study:
- To investigate the function of Tiam1 in neutrophils.
- To understand Tiam1's role in neutrophil adhesion, migration, and effector functions.
- To elucidate Tiam1's unique regulatory mechanism compared to other Rac-GEFs.
Main Methods:
- Analysis of Tiam1 expression in neutrophils.
- Assessment of Tiam1's impact on neutrophil adhesion, actin dynamics, polarization, and migration.
- Evaluation of Tiam1's role in reactive oxygen species generation, degranulation, NETs release, and bacterial killing.
- In vivo studies using mouse models for neutrophil recruitment and bacterial clearance.
- Investigation of Tiam1's effects on Rac1/Rac2 activation and interactions with other small GTPase regulators.
Main Results:
- Tiam1 governs neutrophil focal complexes, actin dynamics, polarization, and migration, influenced by integrin ligands.
- Tiam1 is dispensable for ROS generation but mediates degranulation, NETs release, and bacterial killing in adherent neutrophils.
- In vivo, Tiam1 is essential for neutrophil recruitment and bacterial clearance.
- Paradoxically, Tiam1 restricts neutrophil adhesion to ICAM1 and β2 integrin activity, and limits fMLP-stimulated Rac1/Rac2 activation.
- Tiam1 promotes expression of regulators like αPix, Psd4, Rasa3, and Tiam2, and controls their association with Rac.
Conclusions:
- Tiam1 is a novel regulator of Rac-dependent neutrophil responses, distinct from other known neutrophil Rac-GEFs.
- Tiam1's unique inhibitory roles in adhesion and Rac activation are mediated through its influence on small GTPase regulators.
- Tiam1 plays a critical role in neutrophil-mediated immunity against bacterial infections.
More Related Videos
06:48Live Imaging of Chemokine Receptors in Zebrafish Neutrophils During Wound Responses
Published on: December 4, 2020
2.5K
11:22Quantitative In vitro Assay to Measure Neutrophil Adhesion to Activated Primary Human Microvascular Endothelial Cells under Static Conditions
Published on: August 23, 2013
17.3K
Related Concept Videos
01:17Intracellular Signaling Affects Focal Adhesions
2.7K
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...
Some...
2.7K
01:10Integrins
4.0K
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
4.0K
01:15Activation of Integrins
3.5K
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...
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...
3.5K
01:24Small GTPases - Ras and Rho
4.0K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
4.0K
01:25Selectins
3.3K
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,...
3.3K
01:21Chemotaxis and Direction of Cell Migration
3.4K
Cells can detect chemical cues in their environment and reorganize the cytoskeleton to migrate toward them or away from them. This directional migration, called chemotaxis, is essential during embryogenesis and development, immune response, tissue repair and regeneration, and reproduction. These chemical cues can either attract or repel the cell's movement. For example, axon development is determined by a combination of chemoattractants and chemorepellents that direct the growing axon...
3.4K