Transcript Slide 1
CELL JUNCTIONS Yasir Waheed • Cells are small, deformable , filled with aqueous medium and surrounded by fragile plasma membrane; yet they combine in different manners to form strong and massive structures like a horse or a tree. • The building technologies of animals and plants are different, and each type of organism is formed of many types of tissues, in which the cells are assembled and bound together in different ways. In both animals and plants, however, an essential part is played in most tissues by the extracellular matrix. • In animals, the cells of most tissues are bound directly to one another by cell-cell junctions Figure 19-1. A cross-sectional view of part of the wall of the intestine. This long, tubelike organ is constructed from epithelial tissue (red), connective tissue (green), and muscle tissue (yellow). Each tissue is an organized assembly of cells held together by cellcell adhesions, extracellular matrix, or both. Cell Junctions • Specialized cell junctions occur at points of cell-cell and cellmatrix contact in all tissues, and they are particularly plentiful in epithelia. • Cell junctions can be classified into three functional groups: • 1. 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. • 2. Anchoring junctions mechanically attach cells (and their cytoskeletons) to their neighbors or to the extracellular matrix. • 3. Communicating junctions mediate the passage of chemical or electrical signals from one interacting cell to its partner. Tight Junctions • Tight junctions have this barrier role in vertebrates e.g. the mammalian small intestine. • The epithelial cells lining the small intestine form a barrier that keeps the gut contents in the gut cavity / lumen. At the same time, the cells transport selected nutrients across the epithelium from the lumen into the extracellular fluid, or gut. These nutrients diffuse into small blood vessels to provide nourishment to the organism. Figure 19-2. The role of tight junctions in transcellular transport. Transport proteins are confined to different regions of the plasma membrane in epithelial cells of the small intestine. This segregation permits a vectorial transfer of nutrients across the epithelium from the gut lumen to the blood. 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 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 gut lumen. Figure 19-3. The role of tight junctions in allowing epithelia to serve as barriers to solute diffusion. (A) The drawing shows how a small extracellular tracer molecule added on one side of an epithelium cannot traverse the tight junctions that seal adjacent cells together. (B) Electron micrographs of cells in an epithelium in which a small, extracellular, electron-dense tracer molecule has been added to either the apical side (on the left) or the basolateral side (on the right). In both cases, the tracer is stopped by the tight junction. Figure 19-5. A current model of a tight junction. (A) This drawing shows how the sealing strands hold adjacent plasma membranes together. The strands are composed of transmembrane proteins that make contact across the intercellular space and create a seal. (B) This drawing shows the transmembrane claudin and occludin proteins in a tight junction. Figure 19-6. A septate junction. A conventional electron micrograph of a septate junction between two epithelial cells in a mollusk. The interacting plasma membranes, seen in cross section, are connected by parallel rows of junctional proteins. The rows, which have a regular periodicity, are seen as dense bars, or septa. Anchoring junctions • Anchoring junctions mechanically attach cells (and their cytoskeletons) to their neighbors or to the extracellular matrix. • Anchoring junctions are widely distributed in animal tissues and are most abundant in tissues that are subjected to severe mechanical stress, such as heart, muscle, and epidermis. • Anchoring Junctions are composed of two main classes of proteins. • Intracellular anchor proteins are present on the cytoplasmic face of the plasma membrane and connect the junctional complex to either actin filaments or intermediate filaments. • Transmembrane adhesion proteins have a cytoplasmic tail that binds to one or more intracellular anchor proteins and an extracellular domain that interacts with either the extracellular matrix or the extracellular domains of specific transmembrane adhesion proteins on another cell. Figure 19-7. Anchoring junctions in an epithelium. This drawing illustrates, in a very general way, how anchoring junctions join cytoskeletal filaments from cell to cell and from cells to the extracellular matrix. Figure 19-8. The construction of an anchoring junction from two classes of proteins. This drawing shows how intracellular anchor proteins and transmembrane adhesion proteins form anchoring junctions. • Anchoring junctions occur in two functionally different forms: • 1. Adherens junctions and desmosomes hold cells together and are formed by transmembrane adhesion proteins that belong to the cadherin family. • 2. Focal adhesions and hemidesmosomes bind cells to the extracellular matrix and are formed by transmembrane adhesion proteins of the integrin family. Figure 19-9. Adherens junctions. (A) Adherens junctions, in the form of adhesion belts, between epithelial cells in the small intestine. The beltlike junction encircles each of the interacting cells. Its most obvious feature is a contractile bundle of actin filaments running along the cytoplasmic surface of the junctional plasma membrane. (B) Some of the molecules that form an adherens junction. The actin filaments are joined from cell to cell by transmembrane adhesion proteins called cadherins. The cadherins form homodimers in the plasma membrane of each interacting cell. The extracellular domain of one cadherin dimer binds to the extracellular domain of an identical cadherin dimer on the adjacent cell. The intracellular tails of the cadherins bind to anchor proteins that tie them to actin filaments. These anchor proteins include a-catenin, b-catenin, gcatenin (also called plakoglobin), a-actinin, and vinculin. (C) The structural components of a desmosome. On the cytoplasmic surface of each interacting plasma membrane is a dense plaque composed of a mixture of intracellular anchor proteins. A bundle of keratin intermediate filaments is attached to the surface of each plaque. Transmembrane adhesion proteins of the cadherin family bind to the plaques and interact through their extracellular domains to hold the adjacent membranes together. (D) Some of the molecular components of a desmosome. Desmoglein and desmocollin are members of the cadherin family of adhesion proteins. Their cytoplasmic tails bind plakoglobin (g-catenin), which in turn binds to desmoplakin. Desmoplakin also binds to the sides of intermediate filaments, thereby tying the desmosome to these filaments. (B) Some of the proteins that form focal adhesions. The transmembrane adhesion protein is an integrin heterodimer, composed of an alpha and a beta subunit. Its extracellular domains bind to components of the extracellular matrix, while the cytoplasmic tail of the beta subunit binds indirectly to actin filaments via several intracellular anchor proteins. Figure 19-13. Desmosomes and hemidesmosomes. The distribution of desmosomes and hemidesmosomes in epithelial cells of the small intestine. The keratin intermediate filament networks of adjacent cells are indirectly connected to one another through desmosomes and to the basal lamina through hemidesmosomes. Gap Junctions Most cells in animal tissues are in communication with their neighbors via gap junctions. Each gap junction appears in conventional electron micrographs as a patch where the membranes of two adjacent cells are separated by a uniform narrow gap of about 2 - 4 nm. The gap is spanned by channel-forming proteins (connexins). The channels they form (connexons) allow inorganic ions and other small water-soluble molecules to pass directly from the cytoplasm of one cell to the cytoplasm of the other, thereby coupling the cells both electrically and metabolically. Figure 19-14. Determining the size of a gap-junction channel. When fluorescent molecules of various sizes are injected into one of two cells coupled by gap junctions, molecules with a mass of less than about 1000 daltons can pass into the other cell, but larger molecules cannot. Figure 19-15. Gap junctions. (A) A three-dimensional drawing showing the interacting plasma membranes of two adjacent cells connected by gap junctions. The apposed lipid bilayers (red) are penetrated by protein assemblies called connexons (green), each of which is formed by six connexin subunits. Two connexons join across the intercellular gap to form a continuous aqueous channel connecting the two cells. (B) The organization of connexins into connexons and connexons into intercellular channels. The connexons can be homomeric or heteromeric, and the intercellular channels can be homotypic or heterotypic. Figure 19-17. Gap junction coupling in the ovarian follicle. The oocyte is surrounded by a thick layer of extracellular matrix called the zona pellucida (discussed in Chapter 20). The surrounding granulosa cells are coupled to each other by gap junctions formed by connexin 43 (Cx43). In addition, the granulosa cells extend processes through the zona pellucida and make gap junctions with the oocyte. These gap junctions contain a different connexin (Cx37). Mutations in the gene encoding Cx37 cause infertility by disrupting the development of both the granulosa cells and the oocyte. Figure 19-19. A summary of the various cell junctions found in a vertebrate epithelial cell. The drawing is based on epithelial cells of the small intestine. Figure 19-20. Plasmodesmata. (A) The cytoplasmic channels of plasmodesmata pierce the plant cell wall and connect all cells in a plant together. (B) Each plasmodesma is lined with plasma membrane that is common to two connected cells. It usually also contains a fine tubular structure, the desmotubule, derived from smooth endoplasmic reticulum. THANKS