Tuesday, March 10, 2009


Cadherins (Calcium dependant adhesion molecules) are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium (Ca2+) ions to function, hence their name.

Excellent Videos about Cadherins (I was not able to embed the videos so click on the links below):
Cadherins: Structure and Function Part I ( introduction)
Cadherins: Structure and Function Part II ( Cadherin Molecular Structure and Function )
Cadherins: Structure and Function Part III ( Adherens Junctions and Tissue Morphogenesis )
Cadherins: Structure and Function Part IV ( Cadherins in the Neural Network )
Cadherins: Structure and Function Part V ( Conclusion )

EXCERPT from Seed Magazine article: The Mason's Apprentice

"Multicellularity requires complex cell adhesion and signaling abilities — development and differentiation cannot occur without them. A multicellular organism is made up of cells that stick to one another with varying degrees of strength, which is mediated by an external coat of proteins and sugars that makes cells sticky in specific ways. In addition, cells secrete proteins and sugars that form a kind of fibrous goo called the extracellular matrix, to which they can also stick. When cell proteins bind to other cells or the extracellular matrix, the proteins trigger biochemical changes — the signaling part of the process — that can cause changes in cell metabolism, gene activity, cell shape, and physiology. These capabilities are fundamental to building a multicellular organism.

So where did they come from?

One must be careful when investigating this question not to make an easy but erroneous assumption: that cell adhesion and cell-to-cell signaling are a consequence of multicellularity. They are not. In fact, it turns out that single-celled organisms have a diverse array of mechanisms for interacting with one another, and multicellular life's fancy cell-communication tools are recent appropriations of mechanisms refined by evolution over billions of years, well before the first tiny worm congealed in the late pre-Cambrian.

"Simple" one-celled organisms like bacteria (which aren't simple, except in terms of number of cells) are sensitive to their environment, including the presence of other bacteria, and transduce chemical signals around them into changes in gene activity. The central principles of cell signaling are all in place in E. coli, and we can see the general idea clearly expressed in the rest of the prokaryotes. But another group of single-celled organisms, a group of eukaryotes — are of particular interest to multicellular animals like ourselves because they are the protists most closely related to us. These organisms are pf great interest to evolutionary biologists because they demonstrate that our toolbox of cell-adhesion and signaling proteins are of utility to organisms that don't have tissues and a higher level of organization. These fascinating creatures are the choanoflagellates.

Two particularly significant classes of proteins that animals use for adhesion and signaling are shared between animals and choanoflagellates. One is a group of proteins called cadherins. These are important cell-adhesion molecules that are regulated by calcium in the environment. Before being found in choanoflagellates, cadherins were thought to be unique to animals — plants and fungi do not have them. Another is a group of proteins called integrins that help cells stick to the extracellular matrix. Among other things, these molecules adhere to the collagen in connective tissues; they are essential for holding us together in a coherent form, versus a pile of gooey jelly."

are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium (Ca2+) ions to function, hence their name. The cadherin superfamily includes cadherins, protocadherins, desmogleins, and desmocollins, and more. In structure, they share cadherin repeats, which are the extracellular Ca2+-binding domains.

There are multiple classes of cadherin molecule, each designated with a prefix (generally noting the type of tissue with which it is associated). It has been observed that cells containing a specific cadherin subtype tend to cluster together to the exclusion of other types, both in cell culture and during development. For example, cells containing N-cadherin tend to cluster with other N-cadherin expressing cells. However, it has been noted that the mixing speed in the cell culture experiments can have an effect on the extent of homotypic specificity.[1] In addition, several groups have observed heterotypic binding affinity (i.e., binding of different types of cadherin together) in various assays.[2][3] One current model proposes that cells distinguish cadherin subtypes based on kinetic specificity rather than thermodynamic specificity, as different types of cadherin homotypic bonds have different lifetimes.[4]

Different members of the cadherin family are found in different locations. E-cadherins are found in epithelial tissue; N-cadherins are found in neurons; and P-cadherins are found in the placenta. T-cadherins have no cytoplasmic domains and must be tethered to the plasma membrane.

E-cadherin (epithelial) is the most well-studied member of the family. It consists of 5 cadherin repeats (EC1 ~ EC5) in the extracellular domain, one transmembrane domain, and an intracellular domain that binds p120-catenin and beta-catenin. The intracellular domain contains a highly-phosphorylated region vital to beta-catenin binding and therefore to E-cadherin function. Beta-catenin can also bind to alpha-catenin. Alpha-catenin participates in regulation of actin-containing cytoskeletal filaments. In epithelial cells, E-cadherin-containing cell-to-cell junctions are often adjacent to actin-containing filaments of the cytoskeleton.

E-cadherin is first expressed in the 2-cell stage of mammalian development, and becomes phosphorylated by the 8-cell stage, where it causes compaction. In adult tissues, E-cadherin is expressed in epithelial tissues, where it is constantly regenerated with a 5-hour half-life on the cell surface.

Loss of E-cadherin function or expression has been implicated in cancer progression and metastasis. E-cadherin downregulation decreases the strength of cellular adhesion within a tissue, resulting in an increase in cellular motility. This in turn may allow cancer cells to cross the basement membrane and invade surrounding tissues.

Another is a group of proteins called integrins that help cells stick to the extracellular matrix.

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