Contributor: Assistant Prof Ronen Zaidel-Bar, MBI, Singapore Updated on: March 2013
Reviewer: Under Review
cell-adhesion molecules (CAMs). These proteins contain domains that permit binding to specific partner proteins and in doing so facilitate interactions between apposed cells. CAMs fall into four main groups:
Immunoglobulin superfamily (Ig) CAMs
Members of this family include vascular and neural cell adhesions molecules (VCAM and NCAM), intercellular adhesion molecules (ICAM) and the nectins and nectin-like (Necl) proteins. Nectins in particular are involved in the formation of cadherin-based cell-cell junctions , mediating initial cell-cell contacts via nectin-nectin or nectin-Necl binding and establishing links to the actin cytoskeleton via nectin-afadin binding . Of the four major groups of CAMs, IgCAMs are the only group that function independently of calcium.
This family of glycoproteins includes over 100 members divided into 6 subfamilies; type I classical cadherins, type II atypical cadherins, desmosomal cadherins, flamingo cadherins, proto-cadherins and several ungrouped members. Cadherins can be identified through common motifs in their extracellular domains termed cadherin repeats. Not all cadherins are involved in cell-cell adhesion, though type I and type II cadherins have well established roles in this process . Both of these subfamilies contain cadherin repeats within their extracellular domains, with the outermost cadherin repeats facilitating extracellular interactions with cadherins on apposing cells (trans interactions). Type I cadherins can in addition engage in lateral interactions on the same cell (cis interactions). Intercellular interactions between cadherins can occur between those of the same type (homophilic binding) or a different type (heterophilic binding). Intracellular interactions involve the cytoplasmic domains of the cadherins. In the case of type I cadherins these interactions can be used to identify this subfamily, namely through their ability to bind catenins via their cytoplasmic tails. Catenins form part of the bridge connecting adherens junctions to the actin cytoskeleton. It should be noted that individual cadherin interactions are weak. The strength of cadherin-based adhesive junctions comes from the clustering of multiple, weak cadherin-cadherin interactions .
These CAMs form heterodimers comprising an alpha and beta subunit and are commonly known to facilitate cell-matrix interactions (e.g. at focal adhesions) via their interactions with extracellular matrix proteins. However they are also capable of mediating cell-cell interactions through their interactions with IgCAMs – a process vital in mounting immune responses via leukocytes .
Three members constitute this family, E-selectin (endothelial), L-selectin (leukocyte) and P-selectin (platelet), all of which bind to fucosylated carbohydrates . For example P-selectin on leukocytes binds PSGL-1 (P-selectin glycoprotein ligand-1) on endothelial cells.
 (see Figure below):
Also known as zonula occludens, these junctions are found in epithelial and endothelial cells and primarily function as diffusion barriers. Integral membrane proteins commonly associated with tight junctions include; claudins, occludin, tricellulin and junctional adhesion molecules (JAMs). These proteins facilitate the formation of the anastomosing membrane strands that comprise tight junctions .
These junctions regulate cell shape, maintain tissue integrity and translate actomyosin-generated forces throughout a tissue . A key component of adherens junctions are the transmembrane glycoproteins cadherins, which bind the intracellular proteins p120-catenin and β-catenin, after which α-catenin is recruited by β-catenin. A vast network of adhesion receptors, scaffolding proteins, actin regulators and signaling proteins form a complex network of interactions, which is currently being characterized and has been named the cadhesome [personal communication A/P Ronen Zaidel-bar, MBI, NUS].
Figure: Adherens junctions of hepatocytes. Hepatocyte cells plated on collagen and stained the next day to image newly formed cell-cell contacts. F-actin (green), β-catenin (red), cadherin (dark blue), nuclei (cyan). The overlap of β-catenin and cadherin seen as magenta represents adherens junctions that have formed between apposing cells. These cells were imaged using a Nikon A1Rsi confocal microscope at 100x magnification. [Image captured by Jeffrey Robens, Mechanobiology Institute, Singapore].
These junctions link intermediate filaments (IFs) to the plasma membrane and in doing so provide mechanical stability to cells, which is particularly important for tissues and organs under high mechanical stress, such as the myocardium, skin and bladder. Desmosomes comprise desmosomal cadherins (desmogleins and desmocollins) that facilitate linkage between apposing cells via their extracellular domains and bind other desmosomal components intracellularly via their cytoplasmic tails. Cytoplasmic desmosomal components include plakoglobin and plakophilins, which in turn bind intermediate filaments via desmoplakin .
 and acquired from The Cell: An Image Library under a Creative Commons, Non-commercial, Share Alike Attribution.
In vertebrate epithelia, all three of the aforementioned junctions have defined spatial organizations, with tight junctions located most apically, followed by adherens junctions and lastly desmosomes . Each type of junction has a distinct ultrastructure, which can additionally vary in appearance dependent on cell type and morphology, as illustrated in the Figure below for adherens junctions. The concepts pertaining to the formation of cell-cell contacts in this unit shall be discussed with particular emphasis on adherens junctions.
. This diagram depicts three different examples of adherens junctions; punctum adherens that are common in mesenchymal and neural cells, zonula adherens that are common in endothelial and epithelial cells and Tricellular adherens junction. Common in all cell monolayers .
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