Related Experiment Video
Updated: Jun 20, 2026
09:14
Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
Published on: June 13, 2014
Integrin-alpha9 is required for fibronectin matrix assembly during lymphatic valve morphogenesis.
Eleni Bazigou1, Sherry Xie, Chun Chen
1Lymphatic Development Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Developmental Cell
|August 19, 2009
Summary
Integrin-alpha9 and fibronectin-EIIIA are crucial for lymphatic valve development. Their interaction guides leaflet formation, and defects cause lymphedema.
Area of Science:
- Developmental Biology
- Cell Biology
- Vascular Biology
Background:
- Lymphatic valve dysfunction causes human lymphedema.
- Lymphatic valve development (morphogenesis) mechanisms are not well understood.
Purpose of the Study:
- Investigate the role of integrin-alpha9 and fibronectin-EIIIA in lymphatic valve formation.
- Identify molecular mechanisms underlying lymphatic valve morphogenesis.
Main Methods:
- Utilized mouse models with endothelial cell-specific deletion of integrin-alpha9 (Itga9).
- Examined mice lacking the EIIIA domain of fibronectin (FN).
- Studied primary human lymphatic endothelial cells.
Main Results:
- Integrin-alpha9 upregulation and fibronectin-EIIIA deposition initiate lymphatic valve leaflet formation.
- Deletion of Itga9 or FN-EIIIA domain resulted in rudimentary valve leaflets, disorganized matrix, and impaired lymphatic flow.
- Integrin-alpha9-EIIIA interaction regulates fibronectin fibril assembly for extracellular matrix core formation.
Conclusions:
- Integrin-alpha9 signaling is vital for lymphatic valve morphogenesis.
- Defects in this pathway are implicated in primary lymphedema due to valve abnormalities.
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01:10Integrins
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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,...
01:17Intracellular 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...
01:25Fibronectins Connect Cells with ECM
Fibronectin is an adhesive glycoprotein present in the extracellular matrix of embryogenic and adult tissue. These molecules primarily aid in regulating cell motility and attachment. A fibronectin molecule is composed of two identical polypeptide chains attached to each other by a pair of disulfide bonds at the C-terminal.
Both proteoglycans and collagen are attached to fibronectin proteins, which, in turn, are attached to integrin proteins. These integrin proteins interact with transmembrane...
Both proteoglycans and collagen are attached to fibronectin proteins, which, in turn, are attached to integrin proteins. These integrin proteins interact with transmembrane...
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.
01:03Anchoring Junctions
Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...
01:13Cell-matrix's Response to Mechanical Forces
In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue.
Anchoring junctions mechanically attach a cell to the...
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