howMed Know Yourself
CELL POLARITY
• Epithelial cells exhibit distinct polarity. They have:
– Apical domain, directed towards the exterior surface.
– Lateral domain, communicates with adjacent cells and is characterized by specialized attachment areas.
– Basal domain, rest on the basal lamina anchoring the cell to underlying connective tissue.
• Specific biochemical characteristics are associated with each cell surface.
• The Apical Domain and its modifications
1)Microvilli
• Microvilli are small, slender, fingerlike projections of the apical cell surface formed by tube-like evaginations of the apical plasma membrane, with a core of cytoplasm containing microfilaments of actin.
• Microvilli vary in length and number ad provide an increase in surface area.
• Cells with a principle absorptive function, such as intestinal and kidney tubule epithelia, show closely packed, long, parallel microvilli on their apical surfaces, visible by light microscopy as a brush or striated border.
• In these cells, the terminal web is well developed and appear as a horizontal network of microfilaments lying ing cytoplasm just below the basis of microvilli and extending peripherally to the zonula adherens.
• Actin filaments lie superficially in this network and pass to the zonula.
• Myosin is also present in the terminal web and an actin-myosin interaction results in shortening of microvillus core bundles and contraction of microvilli to aid the absorptive process.
2) Stereocilia, microvilli of unusual length
Limited to epididymus of male reproductive system (absorptive) and sensory hair cells of ear (receptor device
3) Cilia
• The cilia are fine, hair-like processes of the free apical surface of some epithelial cells.
• They may be very numerous for example in respiratory epithelial cells, where they function to transport material (mucus) in one direction along the surface of the membrane.
• Each cilium, undergo a rapid forward beat with a slower recovery stroke.
ON ELECTRON MICROSCOPY
• Contain organized core of Microtubules
• Cross section – 9 pairs of circularly arranged surrounding 2 central microtubules
• 9/2 arrangement is present from the tip to the base
• Dyenin an ATPase is present in microtubule extending from one to the other microtubule
• Basal body is a modified centriole
• Outer paired micro tubule joins the Basal body
• Possess internal structures
Arranged in orderly rows
• Trachea, Bronchi, Oviducts
LIGHT MICROSCOPE
• Short, fine hair like structures
• Thin dark staining, basal band at the base – Basal bodies
• Each cilium has a single Basal body, distinct from others
• Cilia are found in maculae and cristae of the inner ear and in rods of the retina, where they are receptors.
• In other cell types, they occur signally and function possibly as chemoreceptors.
• The single flagellum of spermatozoa is similar in structure to a cilium and is also motile.
MOVEMENT
• regular, sequential and synchronous
Effective stroke
rapid forward movemnt in a rigid state
Recovery stroke
flexible and slower return
Metachronal rhythm
• sequential timings – cilia in successive row start before then the following row
• result – creating a wave that sweeps across the epithelium
• (responsible for movement of fluid, mucus over the epithelial surfaces)
The Lateral Domain and its Specializations in Cell to Cell Adhesion
• The lateral domain is characterized by the presence of unique proteins.
• The lateral surface membrane in some epithelia may form folds and processes, Invaginations and evaginations that create interdigitating and interleaving tongue-and-groove margins between neighboring cells.
• The junctional complexes are responsible for joining individual cells together and contain three types of junctions:
1) Occluding junctions:
• These are also called tight junctions because they are impermeable in nature.
• They form intercellular diffusion barrier between adjacent cells.
• They maintain physicochemical separation of tissue compartments.
• prevent the migration of specialized membrane proteins between the apical and lateral surfaces, thus maintaining the integrity of these two domains.
2) ANCHORING JUNCTIONS :
– provide mechanical stability to epithelial cells by linking the cytoskeleton of one cell to the cytoskeleton of an adjacent cell.
– These junctions are important in creating and maintaining the structural unity of the epithelium.
3) COMMUNICATING JUNCTIONS:
– allow direct communication between adjacent cells by diffusion of small molecules fore example, ions and amino acids and permits the coordinated cellular activity that is important for maintaining organ homeostasis.
Occluding Junctions
• The zonula occludens represents the most epical component in the junctional complex between epithelial cells and is created by localized sealing of adjacent plasma membranes.
• It is not a continuous seal but is a series of focal fusions between the cells.
• The transmembrane protein occludin has been identified as the sealing protein.
Zonula occludens
• Distribution: Fusion sites/strands highly variable (sparse ; kidney tubules- partially permeable, numerous ; intestinal epithelia & urinary bladder- impermeable)
• In some tissues, tight junctions can be disrupted by removing calcium ions or treating with protease.
The zonula occludens separates the luminal space from the intercellular space and connective tissue compartment.
• It plays an essential role in the selective passage of substances from one side of an epithelium to the other
• This transport must occur by active means and requires specialized membrane transport proteins.
• The zona occludens, thus establishes functional domain in the plasma membrane.
Anchoring junctions
• Anchoring junctions provide lateral adhesions between epithelial cells, using proteins that link into the cytoskeletal of the adjacent cells.
• Two types of anchoring cell-to-cell junctions can be identified on the lateral cell surface:
– Zonula adherens, which interacts with the network of actin filaments inside the cell.
– Macula adherens, or desmosome which interacts with intermediate filaments.
• Zonula adherens occurs in a continuous band or belt-like configuration around the cell.
• It is composed of the transmembrane adhesion molecule E-cadherin.
• The extracellular components of the E-cadherin molecule from adjacent cells are linked by calcium ions or an additional extracellular link protein.
• Thus, the morphologic and functional integrity of the zonula adherins is calcium dependant.
• Removal of calcium leads to dissociation of E-cadherin molecule and disruption of the junction.
DESMOSOMES/MACULA ADHERENS
• Spot like attachment structure on the lateral sides
• Not a continous structure around the cell like ZA
• On the cytoplasmic side of plasma membrane is very dense disc shaped material –attachment plaque (desmoplakins & plakoglobins)
• Intermediate filaments attached to attachment plaque
• Intercellular space is wide & =upto 30nm & is occupied by Ca+2 dependent CAMs of Cadherin family
• In epidermal cells only desmosomes are present
• The fascia adherens is a sheet-like junction that stabilizes nonepithelial tissue.
• An exception to this is cardiac muscle cells that are arranged end to end, forming thread-like contractile units(ZA &MA)
• The macula adherens provides localized spot-like adhesion between epithelial cells.
Communicating juntions
• Communicating junctions, also called gap junctions or nexus, are present in a wide variety of tissues, including epithelia, smooth and cardiac muscles, and nerves.
• They are important in tissues in which activity of adjacent cells must be coordinated, such as epithelia engaged in fluid and electrolyte transport, vascular and intestinal smooth muscle, and heart muscle.
• A gap junction consists of an accumulation of transmembrane channels or pores in a tightly packed array.
• The gap junctions allow cells to exchange ions, regulatory molecules, and small metabolites, through the pores.
• Organized concentrations of integral membrane proteins form the gap junctions.
• Gap junctions reduce resistance to passage of electric current between adjacent cells.
The Basal Domain and its Specializations in Cell-to-Extracellular Matrix Adhesion
• The basal domain of epithelial cells is characterized by several features:
– Basement membrane, which is located next to the basal surface of epithelial cells.
– Cell-to-extracellular matrix junctions, which anchor the cell to the extracellular matrix.
– Plasma membranes infoldings, which increase surface area and facilitate morphologic interactions between adjacent cells.
Basement membrane
• The term basement membrane was originally given to a layer of variable thickness at the basal surfaces of epithelia.
• The basal lamina is the structural attachment side for overlying cells and underlying connective tissue.
• Between the basal lamina and the cell is a relatively clear or electron-lucent area, the lamina lucida which contains extracellular portions of cell adhesion molecules mainly fibronectin receptors.
• The basal lamina includes at least four groups of molecules mainly,
• Collagen
• Proteoglycans
• Laminin
• Entactin and fibronectin
• A layer of reticular fibers, underlies the basal lamina. Basal laminae have multiple functions for example:
• Structural attachment
• Compartmentalization
• Filtration
• Polarity induction
• Tissues scaffolding
Cell-to-extracellular matrix junctions
• The organization of cells in epithelium depends on the support provided by the extracellular matrix on which the basal surface of each cell rests.
• Anchoring junctions maintain the morphologic integrity of the epithelium-connective tissue interface. These anchoring junctions are:
– Focal adhesions, which anchor actin filaments of the cytoskeleton into the basement membrane.
– Hemidesmosomes, which anchor the immediate filaments of cytoskeleton into the basement membrane.
HEMIDESMOSOMES
• Location: Variant of desmosomes are located on the inner surface of basal plasma membranes where they provide increased adhesion to the basal lamina.
• Function: Present in epithelia which are subjected to abrasion & mechanical shearing forces that tend to separate epithelia from underlying C.T
• Distribution: The best examples are found in the basal layers of stratified squamous epithelium: Cornea, Skin, Oral cavity, Esophagus, Vagina
• Structure: Half the desmosome
• Attachment plaques – Integrins
• Anchor IF of cytoskeleton
• Extracellular portion of these integrins enter the basl lamina & interact with its proteins laminins & type IV collagen
• Focal adhesions create a dynamic link between the actin cytoskeleton and extracellular matrix proteins.
• Hemidesmosomes occur in epithelia that require strong, stable adhesions to the connective tissue.
Morphologic Modifications of the Basal Cell Surface
• Many cells that transport fluid have infoldings at the basal cell surface for example, proximal and distal tubules of the kidney and in certain ducts of salivary glands.
• Mitochondria are concentrated at this basal side to provide the energy requirements for active transport.
