CELL ADHESION MOLECULES Department of Natural Sciences University of St. La Salle Bacolod City
Major families of cell-adhesion molecules (CAMs) and adhesion receptors.
Dimeric E-cadherins most commonly form homophilic (self) cross-bridges with E-cadherins on adjacent cells. Members of the Immunoglobulin (Ig) superfamily of CAMs can form both homophilic linkages and heterophilic (nonself) linkages. Heterodimeric integrins function as CAMs or as adhesion receptors that bind to very large, multiadhesive matrix proteins such as fibronectin. Selectin dimers contain a carbohydrate-binding lectin domain that recognizes specialized sugar structures on glycoproteins and glycolipids on adjacent cells.
Note that CAMs often form higher-order oligomers within the plane of the plasma membrane. Many adhesive molecules contain multiple distinct domains, some of which are found in more than one kind of CAM. The cytoplasmic domains of these proteins are often associated with adapter proteins that link them to the cytoskeleton or to signaling pathways. The evolution of CAMs, adhesion receptors, and ECM molecules with specialized structures and functions permits cells to assemble into diverse classes of tissues with varying functions.
CADHERINS are a family of single-pass transmembrane glycoproteins which stick embryonic cells together in the presence of calcium (e.g. E-cadherin in epithelial tissues; N- cadherin in neural tissue). Cadherin tails are anchored to actin bundles in the cytoskeleton by a complex called catenins ( -catenin, a component of the Wnt signaling pathway provides a potential link between cell signaling and cell association).
Three glycoproteins mediate Ca+2-dependent cell adhesion: (desmoglein I, desmocollin I and II) and 4 non-glycosolated proteins located in the attachment plaque (desmoplakin I and II, pakoglobin and a basic polypeptide). Abundant in stratified squamous epithelium, which are sites of attachment of the cytoskeleton to the free surface. Although sites of cell to Bullous pemphigold is an autoimmune disease cell adhesion, they do not in which antibodies against desmosomal hamper the flow of proteins are formed. This results in substances between widespread skin & mucous membrane cells. blistering as desmosomal proteins fall apart.
E-cadherin (epithethial tissue), N-cadherin (nervous tissues)and P-cadherin (placental tissue) act to drive the adhesion of cells of particular tissue type
Cadherins are required for development.Blastomeres adhere to each other as a result of ECM proteins the cells express on their surfaces.
CAMs (Cell Adhesion Molecules) are single-pass transmembrane glycoproteins which do not require calcium to bind to other cells. Neural cell adhesion molecules (N-CAMs) are a large family of proteins formed by alternative splicing. When embryonic tissue is exposed to antibodies that interact with N-CAMs, the cells do not bind to each other and neural tissue is not formed. N-CAMs and cadherins mediate cell-cell recognition and cell-cell adhesion.
Their carbohydrate groups determine the strength and specificity of cell-cell recognition and adhesion. N-CAMs have repeating chains of negatively charged sialic acid which changes during development. Expression of low sialic acid molecules on adjacent cell surfaces promote junction formation on the adjacent cell membranes. When the polysialic acid residues are removed, the two cells can adhere. The loss of sialic acid groups from Vesicles with N-CAMs having glycophorin may target old RBC for little sialic acid bind tighter destruction in the spleen. The enzyme neuraminidase can cleave the terminal than those with large sialic acid groups as a mechanism to amounts. identify old RBC for retirement.
INTEGRINS (I-CAMs) are cell surface receptors that bind the ECM. They require (Ca+2 or Mg+2), to interact with ECM components (fibronectin, laminin and collagens). Important in epithelial cell cohesion and attachment to substrate and cell migration during tissue repair. Bound integrins prevent transcription of genes that specify apoptosis.
It consists of 2 large non- covalently bound trans- The fibronectin receptor is the membrane proteins (α and ß best characterized integrin. subunits). A number of bothsubunits combine to produce alarge variety of heterodimeric integrins. On the outer surface, the subunits interact to form a binding site for the adhesive glycoprotein, the RGD sequence of the ECM glycoprotein. Most of the binding specificity depend upon the α subunit. On the cytosolic side, the receptor binds components of the cytoskeleton to enable the ECM to communicate through the plasma membrane to the cytoskeleton.
Binding of integrins to ECM activatessignal transduction pathways.
During inflammation, leukocytes initiate attachment to the endothelial cell surface through the SELECTINS, then stabilize the adhesion through the interaction of an integrin and an ICAM.