cell adhesion

ByPeter Jon Arguez

Cell adhesion is a complex mechanism involved in a variety of processes including cell migration & invasion, embryogenesis, wound healing and tissue remodeling.the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules

proteins located on the cell surfaceinvolved with the binding with other cells or with the extracellular matrix (ECM) in the process called cell adhesioncell adhesion molecules help cells stick to each other and to their surroundings.

Extracellular domains homophilic bindingHomophilic binding allows cells that express the same type of cadherin to recognize and attach to each otherIntracellular domains attach to actin cytoskeleton through catenins so extracellular connections can affect intracellular organizationMutation or downregulation of cadherin is associated with metastasis in cancer.Mechanical agitation in Ca++-free solution is a useful experimental technique to separate tissues into individual cells

Cadherins attach to the actin-based cytoskeketon through anchor proteins including catenins

Cadherins connect cells at a desmosome

Cadherins join adjacent epithelial cells to one another

The next slide shows the events of synaptogenesis A target cell puts out outgrowths called filopodia as one of them approaches a potential presynaptic neurons axon, the two cells become linked by cadherins.In the presynaptic cell, catenins organize a release zone for synaptic vesicles with docking site proteinsIn the postsynaptic cell, catenins form a corral in which receptors collect

Extracellular domain contains multiple subdomains that resemble those of antibody molecules or immunoglobulinsStructure of the subdomains is stabilized by disulfide bonds rather than Ca++, as in cadherins.

a group of Ca2-independent cell-cell adhesion proteins in vertebratesbelong to the immunoglobin(Ig) superfamily of CAMs reflects their particular importance in nervous tissueLike cadherins, N-CAMs primarily mediate homophilic interactions, binding together cells that express similar N-CAM molecules

The adhesive properties of N-CAMs are modulated by long chains of sialic acidIn embryonic tissues such as brain, polysialic acid constitutes as much as 25 percent of the mass of N-CAMs; in contrast, N-CAMs from adult tissues contain only one-third as much sialic acid

A true specific immune system is largely a vertebrate invention but metazoans have had cell adhesion molecules for a long timeantibodies and T-cell receptors evolved from Ig-cell adhesion molecules throughsplice variations that lacked a membrane anchor antibodiesHighly variable extracellular domains antibodies and T-cell receptors

a family of cell adhesion molecules (or CAMsAll selectins are single-chain transmembrane glycoproteins that share similar properties to C-type lectins due to a related amino terminus and calcium-dependent bindingbind to sugar moieties and so are considered to be a type of lectin, cell adhesion proteins that bind sugar polymersBinding is Ca++-dependentSelectins have a major role in inflammation and hemostasis

E-selectin (in endothelial cells)not expressed under baseline conditions, except in skin microvessels, but is rapidly induced by inflammatory cytokines.L-selectin (in leukocytes)smallest of the vascular selectinsexpressed on all granulocytes and monocytes and on most lymphocytesP-selectin (in platelets and endothelial cells)the largest selectinstored in -granules of platelets and in WeibelPalade bodies of endothelial cells, and is translocated to the cell surface of activated endothelial cells and platelets

receptors that mediate the attachment between a cell and the tissues that surround it, such as other cells or the extracellular matrix

Each integrin consists of an alpha and a beta subunitIntegrins connect epithelial cells to their basal lamina or basement membrane muscle cells and neurons to their sheaths, etc.Generally, integrins bind to matrix proteins called fibronectinsIntegrin binding capability is activated by an inside-to-outside process mediated through the cytoplasmic domainIntegrin binding to extracellular ligand can mediate outside-to-inside signals

The basal lamina (lamina - layers), also known as the basement membrane, is a specialised form of extracellular matrix. Organised in three ways: 1. it can surround cells (for example muscle fibres have a layer of basal lamina around them);2. it lies underneath sheets of epithelial cells3. it separates two sheets of cells, such as the endothelial cells of blood vessels and epithelial cells of another tissue. This type of arrangement is found in the kidney glomerulus, where the basal lamina acts as a permeability barrier or sieve.

The exact composition of the basal lamina varies between different types of cellKidneythe basal lamina acts as a molecular filterneuromuscular junctioneparates the nerve cell from the muscle cell at the synapse, and helps to regenerate the synapse after injury, and helps to localise acetylcholine receptors

The basal lamina provides support to the overlying epithelium, limits contact between epithelial cells and the other cell types in the tissue and acts as a filter allowing only water and small molecules to pass through. If the epithelial cells become transformed (cancerous) and become 'malignant', they are able to break through the basement membrane and invade the tissues beneath. This characteristic is one used in the diagnosis of malignant epithelial tumors.