Related Experiment Video
Updated: Jun 21, 2026
09:14
Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
Published on: June 13, 2014
The adapter protein SLP-76 mediates "outside-in" integrin signaling and function in T cells
1Abramson Family Cancer Research Institute, University of Pennsylvania, 415 BRB/421 Curie Blvd., Philadelphia, PA 19104, USA.
Molecular and Cellular Biology
|August 12, 2009
Summary
SH2 domain-containing leukocyte protein of 76 kDa (SLP-76) is crucial for T-cell receptor (TCR) and integrin signaling. SLP-76 relocation to microclusters is essential for T-cell adhesion, revealing distinct signaling pathways.
Area of Science:
- Immunology
- Cell Signaling
- Molecular Biology
Background:
- SH2 domain-containing leukocyte protein of 76 kDa (SLP-76) is a key signaling adapter in T-cell receptor (TCR) pathways.
- Integrins are critical for T-cell adhesion and migration, but their signaling pathways are less understood.
- The role of SLP-76 in integrin-mediated signaling in T cells remains largely unexplored.
Purpose of the Study:
- To investigate the role of SLP-76 in integrin signaling in T cells.
- To determine if SLP-76 mediates signaling downstream of integrins similar to its role in TCR signaling.
- To elucidate the mechanisms of SLP-76 relocalization in response to integrin engagement.
Main Methods:
- Utilized SLP-76-deficient T cells and SLP-76 mutants.
- Stimulated T cells with TCR and integrin ligands.
- Analyzed SLP-76 relocalization to surface microclusters via microscopy.
- Investigated protein-protein interactions using LAT (linker for activation of T cells) and ADAP (adhesion and degranulation-promoting adapter protein).
Main Results:
- SLP-76 deficiency impairs T-cell adhesion to integrin ligands.
- SLP-76 relocalizes to microclusters upon both TCR and integrin stimulation.
- TCR-induced SLP-76 clustering depends on LAT, while integrin-induced clustering involves ADAP.
- SLP-76 mutants unable to bind ADAP fail to support integrin-mediated adhesion.
Conclusions:
- SLP-76 is a critical mediator of integrin signaling in T cells, distinct from its role in TCR signaling.
- SLP-76 recruitment to integrin-initiated complexes occurs via an ADAP-dependent mechanism.
- SLP-76 relocalization is essential for integrin-dependent T-cell functions, including adhesion.
Related Concept Videos
01:15Activation 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 events provide an effective stimulus.
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 events provide an effective stimulus.
01:17Intracellular 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...
Some...
01:10Integrins
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,...
01:25Selectins
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, which...
01:22T Cell Activation and Clonal Selection
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
01:30Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...