22. MODULE 22.pdf

MODULE 22 Polarity of All Epithelia - All epithelia exhibit polarity; the epithelial cells have apical and basolateral membrane domains separated by tight junctions - The cells form a sheet that separates two environments - The basal surface is anchored in the basal lamina, which abuts other tissue...

MODULE 22 Polarity of All Epithelia - All epithelia exhibit polarity; the epithelial cells have apical and basolateral membrane domains separated by tight junctions - The cells form a sheet that separates two environments - The basal surface is anchored in the basal lamina, which abuts other tissues; the apical surface is free of attachment - The cell organelles and cytoskeletons are arranged in accordance with the cell polarity - Loss of polarity may indicate early stages of neoplastic development Basal Lamina - Basal lamina is a type of ECM under all epithelial cell sheets and tubes; it may surround individual muscle cells, fat cells, Schwann cells. - Basal laminae surround cells such as skeletal muscle cells, underlie epithelia, and are interposed between two cell sheets such as in the kidney glomerulus. Basal Lamina and Basal Membrane - Under an electron microscope, there are three layers of basal lamina/membrane: - Lamina lucida - electron-lucent, with little staining - Lamina densa - electron-dense - Lamina reticularis - can be associated with reticular fibers of the underlying connective tissue - Basal lamina consists of the lamina densa and lamina lucida - Basement membrane consists of the basal lamina and reticular lamina Functions - Guides migrating cells to their destinations in development - Creates a scaffold for migrating cells in tissue regeneration - Filters: In the kidney glomerulus, prevents the passage of macromolecules from the blood into the urine - Influences cell polarity, metabolism, and fate - Organizes the proteins in adjacent plasma membranes - Creates a selective barrier to cell movement prevents fibroblasts in the connective tissue from contacting the epithelial cells; however, allows macrophages, lymphocytes, or nerve processes to pass Components of the Basal Lamina - Type IV and type VII collagen - Laminin forms a sheet-like network - Perlecan, a proteoglycan, has a filtering role in the kidney - Entactin/nidogen is a glycoprotein - All proteins bind to each other to make a crosslinked extracellular matrix - Many cell-surface receptors for type IV collagen and laminin are integrins MODULE 22 Laminin Structure - Laminin-1 has three polypeptide chains (α, β, and γ) in the shape of a cross held by disulfide bonds - Laminin binds collagen, perlecan, nidogen (entactin), and laminin receptors on cells Muscular Dystrophy and Defective Basal Lamina - Progressive weakness and degeneration of skeletal muscles - Muscular dystrophy: A group of >30 genetic diseases; ~ half of all cases are Duchenne Muscular Dystrophy (DMD) - Congenital muscular dystrophy is caused by a mutation in laminin α-2 - DMD is caused by a deficit in dystrophin, an intracellular protein that links dystroglycan to the cytoskeleton - Mutations in other components (dystroglycan, α7 integrin, type IV collagen) also cause muscle- wasting diseases Duchenne Muscular Dystrophy (DMD) - DMD is due to mutations in the dystrophin gene (on the X chromosome); mostly male patients; girls are carriers and can be mildly affected - Dystrophin connects the actin cytoskeleton of each muscle fiber to the basal lamina through a dystrophin-associated protein complex (DAPC) - DAPC is destabilized when dystrophin is absent, which results in low levels of the member proteins; this leads to progressive muscle damage Dystrophic Epidermolysis Bullosa - A group of genetic conditions with skin that is fragile and blisters - Blistering affects the hands, feet, knees, and elbows; in severe cases, is widespread, with a high risk of squamous cell carcinoma - Caused by mutated protein used for assembly of type VII collagen - Type VII collagen is a component of the anchoring fibrils of the dermal-epidermal adhesion at lamina densa - Abnormal or missing collagen VII causes separation of the epidermis and dermis, resulting in blisters Putting It Together - Epithelial cells exhibit polarity with apical and basal sides - Epithelial tissues separate two environments and secure the transport between these environments - Basal lamina is a mesh of laminin molecules, where the collagen and laminin are bridged by nidogen and perlecan - Basal lamina is located under all epithelial cell sheets and tubes; may surround individual muscle cells, fat cells, Schwann cells - The basal lamina controls cell migration, acts as a filter, influences cell fate - Mutations in dystrophin result in progressive weakness and degeneration of skeletal muscles