Organ Systems I: Cellular Adhesion and Extracellular Matrix

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CELL JUNCTIONS

CJ's anchor cells to each other and seal the boundaries between the cells. They also form channels for direct transport and communication between cells. There are several kinds.

ANCHORING JUNCTIONS

AJ's are present in all cell types, but esp in tissues that are subject to extreme mechanical stress such as the epithelia of the skin, intestine and uterus. Interactions between cells are mediated by the cytoskeleton. They are important in both adhesion and movement. ADHERENS JUNCTIONS are one type which connect groups of contractile actin filaments through the cell membrane to something outside (for movement), or cells to each other (zona adherens)(for structure). The two major proteins involved are IAP (intracellular attachment proteins) and TLG (transmembrane linker glycoproteins). They are found in the apical region of the cells, and comprise the adhesion junctions in intercalated discs of cardiac muscle tissue.

DESMOSOMES

D'S are button-like structures that connect the intermediate filaments (keratin, etc) of adjacent cells. Different types of cells have different numbers of them. Brain desmosomes are attached to VIMENTIN filaments. Epithelial cells are attached to KERATIN filaments.

A disease: PEMPHIGUS is a disease of autoimmunity that affects the skin. Antibodies destroy the desmosomes and cause blistering and leakage of body fluids into loosened epithelia.

TIGHT JUNCTIONS

Form a tight physical barrier between adjacent cells whose plasma membranes come in direct contact with one another. They prevent the movement of small molecules between two cells, and block the exchange of lipids in membranes that are in direct contact.

GAP JUNCTIONS

Are a hollow cylinder of protein forming a continuous open channel between cells, used for communication via the movement of small water-soluble molecules and ions. Prominent in nerve, brain, cardiac muscle, smooth muscle and liver cells.

THE EXTRACELLULAR MATRIX = ECM

The ECM is a network of proteins surrounding the cells in the body. It was long b elieved to function mainly as inert scaffolding for tissue, but in the early 80's Mina Bissell (Lawrence Berkeley National Laboratory) proposed that ECM is a key "singaling molecule" crucial for normal function cells. She futher postulated that ECM is one of the environmental factors (along with hormones) that communicate with a cell nucleus, modifying neclear structures and leading to selective gene expression. And that ECM is responsible for transmitting environmental signals to cells which affect all aspects of cell life incl proliferation, differentiation and death. Bissell's theory implied that alterations in the ECM or cellular responses to it could lead to malignancy, a radical idea at the time. Her experiments showed that in standard cultures, cancerous breast cells grew at the same rate and took on the same flat appearance as healthy breast cells. But when ECM was added to the culture, the healthy cells once again became plump and round and began sereting milk, whereas the cancerous cells grew wildly into a tumorous mass. Bissell was among the first to connect the regulation of cell growth and development wit the cells environment. This understanding helps wtih the diagnosis and treatment of cancer. This work suggests that even after cancer bgenes have been activated and lesions have formed, it may still be possible to reverse the process and restore the cells to normal appearance and function.

The ECM contains proteoglycans that are approx 90-95% carb and 5-10% protein, and known as GAGs (glycosaminoglycans). They are long and linear and repeat disaccharide units, and are linked to a protein through a common oligosaccharide. The function to form a hydrated gel in which fibrous proteins are imbedded, proving lubrication and shock absorbtion.

Also contains structural proteins such as collagen, elastin and other fibrous proteins. Collage is a triple helix. Elastin is visible in histological slides of arteries.

Last but not least are the adhesion proteins such as FIBRONECTIN which is made by fibroblasts, monocytes and endothelial cells, and contains lots of disulfide bonds. The liver has lots of it, and the spleen has very little. Fibronectin binds to other matrix macromolecules or the cell surface, and functions in blood clotting, wound healing, and general tissue stabilization.

Another adhesion protein is LAMININ, a major glycoprotein in the basal lamina. It forms mats of poly peptide underlying all epithelial cell sheets, and mediates the attachment of cells to connective tissue.

END OF ZWICKEY LECTURE NOTES