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Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.

Anchoring Junctions

Anchoring 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:...

Intracellular Signaling Affects Focal Adhesions

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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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Adherens Junctions

Adherens Junctions

Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types – adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
Adherens Junctions are Dynamic
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The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...

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Related Experiment Video

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Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes

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Published on: June 13, 2014

Eph/ephrin signaling in cell-cell and cell-substrate adhesion.

Arvinder Singh¹, Emily Winterbottom, Ira O Daar

¹Laboratory of Cell and Developmental Signaling, National Cancer Institute-Frederick, Frederick, Maryland 21702, USA.

Frontiers in Bioscience (Landmark Edition)

|December 29, 2011

Summary

Eph receptor tyrosine kinases and ephrin ligands control cell adhesion and tissue development. Dysregulation of this signaling pathway promotes aggressive cancer metastasis.

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Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules

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Published on: October 17, 2014

Area of Science:

Cell biology
Developmental biology
Cancer research

Background:

Cell-cell and cell-matrix adhesion are crucial for tissue formation, development, and cancer metastasis.
While cell adhesion and movement are studied, the signaling mechanisms regulating tissue architecture remain unclear.
Eph receptor tyrosine kinases and their ephrin ligands are key regulators of cell adhesion and motility.

Purpose of the Study:

To elucidate the role of Eph/ephrin signaling in regulating cell adhesion, motility, and tissue architecture.
To understand how Eph/ephrin signaling influences tissue separation and morphogenesis.
To investigate the link between Eph/ephrin signaling dysregulation and cancer progression.

Main Methods:

The study likely involves molecular biology techniques to investigate Eph/ephrin signaling pathways.
Methods may include cell culture, genetic manipulation, and imaging to observe effects on cell adhesion and migration.
Analysis of signaling cascades downstream of Eph receptors and their interaction with ephrin ligands.

Main Results:

Eph/ephrin signaling pathways are identified as critical regulators of cell-cell adhesion and cell motility.
These pathways play a significant role in tissue separation and the process of morphogenesis during development.
Evidence suggests that the de-regulation of Eph/ephrin signaling is associated with increased tumor aggressiveness and metastasis in human cancers.

Conclusions:

Eph/ephrin signaling is a central system for controlling tissue architecture and cell behavior.
Understanding these pathways is vital for both developmental biology and cancer research.
Targeting Eph/ephrin signaling may offer therapeutic strategies for aggressive and metastatic tumors.