L 26 Cytoskeleton & Intercellular Junctions PDF

26 Cytoskeleton & intercellular junctions ILOs By the end of this lecture, students will be able to 1. Correlate stable nature of IM to its supportive role in the cell. 2. Discuss the significance of cellular specificity of the IM in diagnosis of tumors origin. 3....

26 Cytoskeleton & intercellular junctions ILOs By the end of this lecture, students will be able to 1. Correlate stable nature of IM to its supportive role in the cell. 2. Discuss the significance of cellular specificity of the IM in diagnosis of tumors origin. 3. Deduce structural adaptation of the cell junction to its function. 4. Interpret the impact of molecular structure abnormality on tissue integrity. Intermediated Filaments ⮚ These rope-like intermediate filaments are constructed of tetramers of rod-like proteins that are tightly bundled into long helical arrays (Fig 1). Fig 1. Molecular structure and organization of Intermediated filaments ⮚ The individual subunit of each tetramer differs considerably for each type of intermediate filament. The categories of intermediate filaments include keratins, desmin, vimentin, glial fibrillary acidic protein, neurofilaments, and nuclear lamins. Page 1 of 4  Examples of Intermediate Filaments Found in Eukaryotic Cells. Filament Type Cell Type Examples Keratins Epithelium Both keratinizing and nonkeratinizing epithelial cells Desmin Muscle Striated and smooth muscle (except vascular smooth muscle) Gilial fibrillary acidic Glial cells Astrocytes proteins Neurofilaments Neurons Nerve cell body and processes The intercellular junctions These are specialized attachment areas (cell junctions) present on cells that are in close contact with each other. Morphologically, they are classified into three types: a) Zonula (belt-like) junctions completely encircle the cells. b) Fascia (sheet- like) junctions form broad areas of contact between cells. c) Macula (disc-like) junctions are like spot welds on the cell surface. According to their function, the common cell junctions are: 1. Occluding junctions: function in joining cells to form an impermeable barrier, preventing material from taking an intercellular route in passing across the cellular sheath. Page 2 of 4  2. Anchoring junctions (zonula and macula adherens) function in maintaining cell-to-cell or cell-to-basal lamina adherence, thus provide mechanical stability in tissues subjected to mechanical pressure. 3. Communicating junctions: function in permitting movement of ions or signaling molecules between cells, thus coupling adjacent cells both electrically and metabolically. According to their molecular structure, they include: I- Zonula occludens (tight junctions): They form a "belt-like" junction that encircles the entire circumference of the cell. It is established by fusion of the outer layers of the cell membranes of the two cells in an interrupted pattern, where fusion is represented by focal points. (Fig. 1) At the fusion sites, transmembrane junctional proteins called claudins and occludins bind to each other, thus forming a seal occluding the intercellular space. A third transmembrane protein called cadherin reinforces the other two types. (Fig 2) II- Zonula adherentes The intercellular space of 15 to 20 nm between the outer leaflets of the two adjacent cell membranes is occupied by the extracellular moieties of cadherins. (Fig 2) These Ca2+-dependent integral proteins of the cell membrane are transmembrane linker proteins. Their intracytoplasmic aspect binds to a specialized region of the cell web, specifically a bundle of actin filaments. III- Desmosomes (macula adherentes) These "spot weld"-like junctions that are randomly distributed along the lateral cell membranes of adjacent cells. (Fig 1) Disk-shaped attachment plaques are located opposite each other on the cytoplasmic aspects of the plasma membranes of adjacent epithelial cells. (Fig 2) Each plaque is composed of a series of attachment proteins. Intermediate filaments of cytokeratin are observed to insert into the plaque, where they make a hairpin turn, then extend back out into the cytoplasm. IV- Gap junctions (Nexus) Gap junctions are built by six closely packed transmembrane channel-forming proteins (connexins) that assemble to form channel-structures called connexons, aqueous pores through the plasma membrane that juts out about 1.5 nm into the intercellular space. (Fig 2A) Page 3 of 4 When a connexon of one plasma membrane is in register with its counterpart of the adjacent plasma membrane, the two connexons fuse, forming a functional intercellular hydrophilic communication channel. Page 4 of 4