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Related Concept Videos

Activation of Integrins01:15

Activation of Integrins

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Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
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Intracellular Signaling Affects Focal Adhesions01:17

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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.
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Integrins01:10

Integrins

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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.
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Activation and Inactivation of G Proteins01:22

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Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
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IP3/DAG Signaling Pathway01:11

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Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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Related Experiment Video

Updated: Jun 25, 2025

Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
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Ligand binding initiates single-molecule integrin conformational activation.

Jing Li1, Myung Hyun Jo2, Jiabin Yan3

  • 1Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

Cell
|May 21, 2024
PubMed
Summary
This summary is machine-generated.

Integrin activation begins with outside-in signaling upon ligand binding, followed by inside-out signaling. Tensile force transmission through the actin cytoskeleton is crucial for full integrin activation.

Keywords:
FRETinside-out signalingintegrin activation pathwayintegrin conformational changesintegrin conformational dynamicsligandoutside-in signalingsingle moleculetalin

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Fluorescence Biomembrane Force Probe: Concurrent Quantitation of Receptor-ligand Kinetics and Binding-induced Intracellular Signaling on a Single Cell
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Fluorescence Biomembrane Force Probe: Concurrent Quantitation of Receptor-ligand Kinetics and Binding-induced Intracellular Signaling on a Single Cell
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Fluorescence Biomembrane Force Probe: Concurrent Quantitation of Receptor-ligand Kinetics and Binding-induced Intracellular Signaling on a Single Cell

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Area of Science:

  • Cell biology
  • Biophysics
  • Molecular dynamics

Background:

  • Integrins are crucial cell surface receptors mediating cell adhesion and migration by connecting the extracellular matrix to the actin cytoskeleton.
  • Rapid communication between the extracellular environment and the cell's interior is vital for cellular processes.
  • Understanding the conformational changes of integrins upon ligand binding and cytoskeletal interaction is key to deciphering cell signaling.

Purpose of the Study:

  • To investigate the dynamic conformational changes of integrins upon ligand binding and talin interaction.
  • To elucidate the sequence and mechanism of integrin activation initiated by outside-in and inside-out signaling.
  • To determine the role of talin and cytoskeletal tension in integrin activation.

Main Methods:

  • Single-molecule fluorescence dynamics were employed to observe integrin conformational states in real-time.
  • Analysis focused on ligand binding events and subsequent structural rearrangements.
  • The influence of talin binding on integrin conformation was assessed.

Main Results:

  • Ligand binding to the predominant bent-closed integrin conformation triggers rapid (millisecond timescale) leg extension and headpiece opening, forming the high-affinity state.
  • The extended-closed conformation can be accessed directly from the extended-open state, facilitating ligand dissociation.
  • Talin binding alone modestly stabilizes integrins but does not induce the conformational extension or opening necessary for activation.
  • Integrin activation involves a sequential process initiated by outside-in signaling, followed by inside-out signaling.

Conclusions:

  • Integrin activation is a multi-step process initiated by extracellular cues and modulated by intracellular components.
  • Talin binding is necessary but not sufficient for inside-out integrin activation; transmission of tensile force through the actin cytoskeleton is essential.
  • The findings provide a dynamic model for integrin conformational changes and activation mechanisms, highlighting the interplay between external forces and intracellular signaling pathways.