Related Experiment Video
Updated: Jun 19, 2026
09:14
Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
Published on: June 13, 2014
Outside-in signal transmission by conformational changes in integrin Mac-1
Craig T Lefort1, Young-Min Hyun, Joanne B Schultz
1Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY 14642, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|October 30, 2009
Summary
Global conformational changes in Mac-1 integrin are critical for transmitting signals into cells, influencing cell behavior and survival. This study shows structural changes, not just clustering, drive these essential outside-in signals.
Area of Science:
- Cell biology
- Immunology
- Biochemistry
Background:
- Integrins, like Mac-1, are crucial cell surface receptors involved in cell adhesion and signaling.
- Outside-in signaling, initiated by ligand binding to integrins, regulates vital cellular processes.
- The precise structural mechanisms by which integrins transmit these signals remain incompletely understood.
Purpose of the Study:
- To investigate whether conformational changes in Mac-1 integrin are sufficient to mediate outside-in signal transduction in human neutrophils.
- To elucidate the structural basis of Mac-1-mediated signaling.
Main Methods:
- Utilized fluorescence resonance energy transfer (FRET) to monitor conformational changes in Mac-1.
- Analyzed intracellular protein tyrosine phosphorylation patterns, including Akt phosphorylation.
- Assessed the impact on spontaneous neutrophil apoptosis.
Main Results:
- Mac-1 conformational activation, induced by ligand (ICAM-1) or activating antibody binding, triggered specific protein tyrosine phosphorylation patterns.
- These conformational changes, distinct from integrin clustering, inhibited spontaneous neutrophil apoptosis.
- Observed switchblade-like extension of the Mac-1 extracellular domain and separation of cytoplasmic tails upon activation.
Conclusions:
- Global conformational changes in Mac-1 are critical and sufficient for initiating outside-in signal transduction.
- These structural rearrangements are key to regulating neutrophil survival and potentially other cellular functions.
- The findings highlight the primacy of integrin global conformation in signal generation.
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,...
01:26Signal Transduction: Overview
Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Typically, signal transduction involves three...
01:31Immunoglobulin-like Cell Adhesion Molecules
Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
01:21Cell-surface Signaling
Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects.