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Cell and Systems Biology
Maurice Ringuette

Lecture 2 Notes January 12, 2011 th Notes taken verbatim from Alberts 4 and 5 edition unless otherwise noted. Apical Junctions: Tight and ad`herens junctions Introduction Cell adhesion can be subdivided into two broad categories: cell-cell and cell-matrix interactions. The cell adhesion molecules (CAMs) that mediate these interactions have a variety of functions beyond serving as static adhesive elements. For examples, some CAMs act as signal receptors that elicit changes in cell shape and gene expression. Intracellularly, these transmembrane receptors molecules are linked to complexes that play a direct role in signal transduction pathways. As with signal transduction pathway, cell adhesion involves a combination of different CAMs acting at the same time. The information must be integrated for proper development and tissue homeostasis to be maintained In other words, multiple parallel interactions are occurring at the same time and the information generated must be integrated. There here are six major types of tissues: Nerve Muscle Epithelia Connective Most text classify blood and lymphoid tissues as Blood connective tissues Lymphoid What is the difference between junctional and non-junctional adhesion? Junctions are often visualized by conventional or freeze-fracture electron microscopy. In vertebrates, intercellular adhesion of epithelial cells at the apical end is primarily mediated by two types of apical junctional complexes (APJs): tight junctions (TJs) and adherens Junctions (AJs). At the basal end, desmosomes serve to anchor epithelial cells to basal laminae [a specialized extracellular matrix (ECM) sheet we will discuss extensively in later lectures]. Occluding junctions: tight junctions (TJs) TJs are also often referred to as apical junctions because of their location at the apical end of epithelial cells. The main function of TJs is to act as paracellular sealants/barriers between adjacent epithelial cell and endothelial cells, ensuring homeostasis. In multicellular organisms, homeostasis is dependent of being able to isolate the internal environment from the external environment. In addition, distinct internal fluid compartments must also be isolated from each other, e.g. lymphatic and vascular systems. Cellular sheets of epithelia, endothelia and mesothelia establish tissue compartmentalization. Cellular sheets can be simple monolayers (e.g. gut epithelia) or stratified (e.g. skin), the latter being less polarized than the former. Focusing of polarized epithelial sheets, TJs form a branching network of sealing strands that completely encircles the apical end of adjacent cells in an epithelial sheet (Figures 19-25 and 19-26A). Each TJ strand is embedded in the lipid bilayer and forms a tight lateral association with another TJ strand on the 1opposing membrane of an adjacent cell, at the apical-lateral end. The resultant paired strands reduce the intercellular distance to almost zero. The ability of TJs to restrict paracellular diffusion increases logarithmically with the number of strands in the network- suggesting the strand act independently. There is a positive correlation between the number of strands and the tightness of the epithelium. Tight TJs have on average 5 or more strands, whereas leaky TJs often have only one strand. Diffusion between epithelial cells is referred to as paracellular diffusion/secretion. While TJs function as intracellular sealants to prevent paracellular diffusion of ions across epithelia, they show ionic charge and size selectivity depending on the cell type and physiological requirements. At present, two functionally distinct pathways have been identified: a high capacity, charge-selective pore pathway that permits the passage of small ions and uncharged molecules. The second is a low- capacity leak pathway that allows flux of larger ions and molecule independent of charge. Small ions do not discriminate between the pore and leak pathways. +s noted in your text, TJs associated with the gut epithelia are 10,000 times more permeable to Na ions than epithelia lining the bladder wall. Another critical function of TJs is to prevent lateral diffusion (intermixing) of membranes associated proteins and lipids from the apical to basal end of epithelial cells and vice versa. Moreover TJs act as regulators of epithelial cell proliferation and differentiation by recruiting to the apical domain signaling molecules. Indeed, a recurring theme in molecular biology is that most proteins have diverse context-dependent functions. As our technologies become more sophisticated, their diverse functions become more evident. TJs are composed of three classes of evolutionarily conserved transmembrane proteins: claudins, occludins, and ZO (Zona Occludin) proteins. The best studied is the claudin family, which consists of at least 24 members in mice and humans and is the focus of cou
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