Cell Junctions Specialized cell junctions occur at points of cell-cell and cell-matrix contact in all tissues, and they are particularly plentiful in epithelia. Cell junctions can be classified into three functional groups: + Occluding junctions seal cells together in an epithelium in a way that prevents even small molecules from leaking from one side of the sheet to the other. ‘+ Anchoring junctions mechanically attach cells (and their cytoskeletons) to their neighbors or to the extracellular matrix, + Communicating junctions mediate the passage of chemical or electrical signals from one interacting cell to its partner. + QccLUDING JUNCTIONS ‘tight junctions (vertebrates only) 2.septate junctions (invertebrates mainly) + ANCHORING JUNCTIONS + Actin filament attachment sites 41. celkcell junctions (adherens junctions) 2. cell matrix Junctions (focal adhesions) + Intermediate flament attachment sites 1. celkcell junctions (desmosomes) 2. celmatrix junctions {hemidesmosomes) + COMMUNICATING JUNCTIONS 1. gap junctions 2. chemical synapses 3. plasmodesmata (plants only) + Occluding Junctions — Tight Junction (zonuta occludens) — + Form a Selective Permeability Barrier Across Epithelial Cell Sheets+The tight junctions between epithelial cells have two roles. 1. Function as barriers to the diffusion of some membrane proteins (and lipids) between apical and basolateral domains of the plasina membrane , Mixing of such proteins and lipids occurs if tight junctions are disrupted. 2. Seal neighboring cells together so that, if @ low-molecutar-weight tracer is added to one side of an epithetlum, tt will generally not pass beyond the tight junction. + Permeability to small molecules varies greatly In different epithelia. ‘+ Tight junctions in the epithelium fining the small intestine, for example, are 10,000 times more permeable to inorganic fons, such as Na, than the tight junctions in the epithelium lining the urinary bladder. PROTEINS IN TIGHT JUNCTION ‘The major transmembrane proteins in a tight junction are the + dlaudins, which are essential for tight Junction formation and function and differ in different, tight junetions, A second major transmembrane protein in tight junetions Is “ ceeludin, the function of which Is uncertain, “ Claudins and occludins associate with Intracellular peripheral membrane proteins celled ZO proteins (a tight junction is also known as azonuta occludens), which anchor the strands to the actin cytoskeleton + Ininvertebrates, septate junctions are the main occluding junction. The role of tight junctions in transcellular transport In the example shown, glucose is actively transported into the cell by Na-driven glucose symports at the apical surface, and it diffuses out of the cell by facilitated diffusion mediated by glucose carriers in the basolateral membrane. Tight junctions are thought to 4 confine the transport proteins to their appropriate membrane domains by acting as diffusion barriers within the lipid bilayer of the plasma membrane; + these junctions also block the backflow of glucose from the basal side of the epithelium into the gutlumenNa*-driven glucose symport of adjacent cells intercellular space passive glucose carrier protein basolateral surface, Va extracellular fluid —— BLOOD Adherens Junction + Adherens junctions are also referred to as zonula adherens, intermediate junction, or as belt desmosomes. Zonula means small zone or belt-like, and adherens refers to adhesion (sticking together).+ Adherens junctions are built primarily from cadherins, whose extracellular segments bind to each other and whose intracellular segments bind to catenins. Catenins are connected to actin filaments. + Provides a strong bond between the sides of adjacent epithelial cell membranes, Structure and Composition ‘The zonula adherens is composed af several different proteins: +The actin microfilaments of the cytoskeleton (the internal skeleton of the cell}. + Anchor proteins, found inside each cell. These are called catenin, vineulin, and alpha-actinin, ‘They link the actin microfilaments to the cadherins. + Cadherins, namely E-cadherin. These are transmembrane adhesion proteins, whose main portions are located in the extracellular space. + The extracellular part of one cell's cadherin binds to the extracellular part of the adjacent cell's cadherin in the space between the two cells, + This intracellular (within the cell) tail then links up to catenin proteins to form the cadherin-catenin complex. This complex binds to vinculin and alpha-actinin - these two proteins link the cadherin-catenin complex to the cell's internal skeletal framework (the actin microfilaments). RGRGrenS TUNCHON] tyemenetene Desmosomes + Desmosomes are a type of anchoring junction in animal tissues that connect adjacent cells. + Desmesomes have intermediate filaments in the cells underneath that help anchor the junction+ Pemphigus is an autoimmune disease in which the patient has developed antibodies against proteins (cadherins) in desmosomes. The loosening of the adhesion between adjacent epithelial cells causes blistering Function of Desmosomes + The function of desmosomes is to adhere cells together. ‘+ They are found in high numbers in tissues that are subject to a lot of mechanical forces. + For example, many are found in the epidermis, which is the outer layer of skin, and the myocardium, which is muscle tissue in the heart, + They are also found in between squamous epithelial cells, which form the lining of body parts like the heart, blood vessels, air sacs of the lungs, and esophagus. + Numerous studies have characterized roles for desmosomal proteins in the regulation of different signaling pathways. Structure Proteins from three main families coordinate to perform this function . + The junction has a dense cytoplasmic plaque composed of a complex of intracellular anchor proteins, plakogiobin and desmoplakin that are responsible for connecting the cytoskeleton intermediate filament to the transmembrane adhesion proteins. + These adhesion proteins, desmoglein and desmocollin like those at an adherens junction, belong to the cadherin family. + They Interact through their extracellular domains to hold the adjacent plasma membranes together. + Desmoglein and desmocollin are members of the cadherin family of adhesion proteins. Their cytoplasmic tails bind plakoglobin (y-catenin), which in turn binds to desmoplakin. Desmoplakin also binds to the sides of intermediate filaments, thereby tying the desmosome to these filaments.dermogieig __deamocoltin ‘CYTOPLASM plakogtobia desmaplakin wo Intermediate filaments o-caterin Cosherins Gap Junctions + Gap junetions in animal cells are like plasmodesmata in plant cells in that they are channels between adjacent cells that allow for the transport of ions, nutrients, and other substances that enable cells to communicate ‘+ This channel is big enough to allow small molecules such as inorganic fons, and other small ‘water soluble molecules (smaller than 1000kDa) to pass between the cells. However the channel Is too small for proteins, nuclele acids or sugars to pass through.Plasma membranes Intereettutar spac; 24 0M SECC Hy ampnilic channel + The membranes of two adjacent cells are separated by a uniform narrow gap of about 24 nm + maximal functional pore size for the connecting channels of about 1.5 nm + Gap junctions develop when a set of six proteins (called connexins) in the plasma membrane arrange themselves in an elongated donut-like configuration called a connexon. + When the pores {“doughnut holes”) of connexons in adjacent animal cells align, a channel between the two cells forms, ‘+ Gap junctions are particularly important in cardiac muscle: The electrical signal for the muscle to contract Is passed efficiently through gap junctions, allowing the heart muscle cells to contract in tandem. Examples:The action potential in heart (cardiac) muscle flows from cell to cell through the heart providing the rhythmic contraction of the heartbeat, + At some so-called electrical synapses in the brain, gap junctions permit the arrival of an action potential at the synaptic terminals to be transmitted across to the postsynaptic cell without the delay needed for release of a neurotransmitter, + As the time of birth approaches, gap junctions between the smooth muscle cells of the uterus enable coordinated, powerful contractions to begin.‘Several inherited disorders of humans such as certain congenital heart defects and certain cases of congenital deafness have been found to be caused by mutant genes encoding conn s. Plasmodesmata Plasmodesmata (singular, plasmodesma ) are cytoplasmic channels thet pass through the cell walls of adjacent cells, Plasmodesmata are lined by plasma membrane and usually contain a dense central structure, ‘the desmotubule, derived from the smooth endoplasmic reticulum of the two cells, Like gap junctions between animal cells, plasmodesmata serve as sites of cell-to-cell communication, as substances pass through the annulus surrounding the desmotubule plasmodesmata allow much larger molecules (up to SOkDa) to pass between cells, plant viruses spread from one cell to anther through plasmodesmata Plasmodesmata have been shown to transport proteins {inclucing transcription factors), short interfering RNA, messenger RNA, viroids, and viral genomes from cell to cell Plasmodesmata provide an easy route for the movement of ions, small molecules like sugars and amino acids, and even macromolecules like RNA and proteins, between cells, The larger molecules pass through with the aid of actin flaments, smooth endoplasmic reticulum — desmotubule cell walls of adjacent plant cells ae cytosol : plasma membrane lining plasmodesma, connecting two adjacent cells