Lecture 15.2: Tight Junctions

Tight junctions Tight (occluding) junctions More than 60% of the cell types in vertebrate body are epithelial All epithelia are structurally polarized: basal side is attached to the basal lamina and apical surface is bathed in extracellular fluid All epithelia serve as permeability barriers. The occluding junctions seal the cells together to prevent leakage Occluding junctions are also called tight junctions in vertebrate epithelia Two functions of the tight junctions in epithelium of the small intestine Tight junctions provide a selective permeability barrier between cells: selective molecules can pass through, depending on tissue and condition Tight junctions prevent mixing of plasma membrane components: Active transporters the pump glucose in the cell on the apical surface Passive transporters that pump glucose in tissue on the basolateral surface The transport through the cell is called transcellular passport Paracellular transport through the tight junctions The tight junctions can be transiently changed to allow the passage of water and small molecules like amino acids and monosaccharides The transport through the tight junctions is called paracellular transport. It is a passive passage of small molecules in case their concentration in the lumen is very high Paracellular transport requires ATP • A. True • B. False Tight junction is formed by claudins and occludins Claudins and occludins are transmembrane proteins that form the tight junctions They interact by homophilic interactions Each tight junction is composed of a long row of claudins and occludins Claudin molecules can also form paracellular pores, selective channels, allowing specific ions to pass in between the cells Example: Mg2+ in kidney ZO proteins serve as a scaffold for tight junctions ZO (zonula occludins) proteins have multiple domains serving as a scaffold that can bind different components of tight junctions and actin Gap junctions Present in most animal tissues, including connective tissues and epithelia Allow the cells to communicate with their neighbors Are the channels between the cells Allow small water-soluble molecules (inorganic salts, sugars, amino acids, nucleotides, vitamins, cAMP, IP3) to pass between the cells. Molecules larger than 1000 dalton (1 Da = 1 g/mol) cannot pass The structure of gap junctions Gap junctions are assembled from the transmembrane proteins connexins The connexon hexamer forms a half-channel connexon When two channels align they form a continuous channel 1.5 nm in diameter Opening and closing of gap junctions can be regulated Each gap junction is a cluster of a few to many thousands connexons Gap junctions between fibroblasts in culture There are also many semi-channels connexons in the membrane which are in closed conformation. They are used for remodeling the channels The half life of a connexon is only about half an hour; the new connexons are added from the side and old ones are degraded Examples of gap junctions functions Electrical coupling of neurons, which is faster than synapse (escape responses in fish and insects) Synchronous contractions of heart and smooth muscle cells Coordination of responses (liver cells) Development of the egg (follicle cells) A defect in a certain connexon is a common cause of deafness Selectins, a special type of cell adhesion molecules (CAMs) involved in immune response A system to direct immune system cells to other point of infection Selectins bind to oligosaccharides on other cell surfaces The structure of selectin Lectin domain binds oligosaccharides Selectins are calcium dependent Selectins are also named according to cell type L-selectin — leukocytes P-selectin — platelets E-selectins — endothelial cells (blood vessels lining) Selectins make white blood cells roll along the blood vessel walls Weak adhesion and rolling (selectin-dependent) Strong adhesion and emigration (integrin-dependent) One more type of CAMs: immunoglobulin superfamily Contain Ig-like domains Not calcium-dependent Some participate in homophilic binding (to another Ig-like), others in heterophilic binding (to integrins) Bind weaker, then cadherins Serve to fine-tune binding The variable forms of extracellular matrix Bones and teeth Transparent cornea Tendons Where does extracellular matrix come from? Extracellular matrix is secreted by cells of fibroblast family Components of extracellular matrix Proteoglycans, glucosaminoglycans (GAGs) Fibrous proteins (mostly collagen) Glycoproteins GAGs GAG is a repeated disaccharide, non-branched GAGs are highly negatively charged They are fairly stiff and don’t fold into globules like proteins do Examples: hyaluronan, heparin sulfate Hyaluronan consists of about 25,000 sugar monomers Proteoglycans and Hyaluronan form hydrating gels Hyaluronan is very negatively charged It attracts positively charged ions to it The influx of sodium is followed by influx of water because of osmotic pressure Hyaluronan is a component of joint fluid and is massively produced in wound healing Proteoglycans Consist of polysaccharide GAG linked to protein Polysaccharide is linked to serine amino acid Hyaluronan is a _____ • A. GAG • B. Glycoprotein • C. Proteoglycan Collagens Major proteins of extracellular matrix 25% of protein mass in skin and bone 3-stranded, 3 alpha chains Every third residue is glycine (-H) 25 alpha chains, 20 types of collagen Stiff; assemble into fibrils outside the cell Fibrils often assemble into fibers Resist tensile forces Elastin gives tissues their elasticity Hydrophobic protein Cross-linked Fibronectin and other multi domain glycoproteins help organize the matrix Glycoproteins contain multiple copies of protein interaction domains Help organize the matrix and help cells attach to it Guide cell movement