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Related Concept Videos

Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
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Structure of Cadherins01:25

Structure of Cadherins

The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins”   is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This diversity of cadherins...
Adherens Junctions01:24

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.
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Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
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Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Anchoring Junctions01:03

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:...

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Related Experiment Video

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Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules
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E-cadherin interactions are required for Langerhans cell differentiation.

Nobuko Mayumi1, Eri Watanabe, Yoshihiko Norose

  • 1Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan.

European Journal of Immunology
|November 9, 2012
PubMed
Summary

Epidermal E-cadherin is essential for Langerhans cell (LC) differentiation. This protein, expressed by keratinocytes, guides LC development in the skin's epidermis, influencing key cell markers.

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Area of Science:

  • Immunology
  • Dermatology
  • Cell Biology

Background:

  • Human skin harbors two distinct dendritic cell (DC) subsets: epidermal Langerhans cells (LCs) and dermal DCs.
  • LCs express Langerin and are found in the epidermis, while dermal DCs express DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and reside in the dermis.
  • The role of epidermal localization in LC differentiation remains unclear.

Purpose of the Study:

  • To investigate the role of E-cadherin, expressed by epidermal keratinocytes (KCs), in the differentiation of LCs.
  • To determine if E-cadherin provides environmental cues for LC differentiation within the epidermis.

Main Methods:

  • Monocytes were differentiated into LC-like cells using IL-4, GM-CSF, and TGF-β1.
  • LC-like cells were co-cultured with keratinocytes expressing E-cadherin or with recombinant E-cadherin.
  • The expression of Langerin and DC-SIGN was analyzed in LC-like cells.
  • LC-like cells were pretreated with an anti-E-cadherin antibody to assess the necessity of E-cadherin interactions.

Main Results:

  • Monocyte-derived LC-like cells expressed both Langerin and DC-SIGN.
  • Co-culture with E-cadherin-expressing KCs or recombinant E-cadherin reduced DC-SIGN expression and induced an LC phenotype.
  • Anti-E-cadherin antibody treatment abolished Langerin expression, highlighting the importance of E-cadherin interactions for LC differentiation.

Conclusions:

  • E-cadherin expressed by epidermal keratinocytes is crucial for the differentiation of Langerhans cells.
  • E-cadherin provides essential environmental cues within the epidermis that promote LC differentiation.
  • These findings elucidate a key mechanism regulating the development of epidermal LCs.