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48 Cards in this Set

  • Front
  • Back
Intestine order
1. Lumen of gut
2. Epithelium (microvilli)
3. Connective tissue (fibroblasts)
4. Circular fibers (smooth muscle)
5. Longitudinal fibers (smooth muscle)
6. Connective tissue
7. Epithelium (absorb nutrients)
Blood vessels and ducts
1. Endothelial cells line on inside
2. Held together by cell-cell contacts
3. Impermeable barrier
4. Basement membrane supports
Parts of epithelium
apical=top, sides/bottom=basolateral
Polarized cell
epithelial cells are polarized because the apical side is different from teh basolateral
Specialized functions of epithelia
1. Uptake (nutrients, gases, wastes)
2. Secretion (hormones, milk)
3. Separation of functional liquids
5 major epithelial cell junctions
1. Tight junction
2. Adherens junction
3. Desmosome
4. Gap junction
5. Hemidesmosome
Tight junction (function)
seals neighboring cells together in an epithelial sheet to prevent leakage of molecules between them, very close apposition of adjacent cells, separates the apical and basolateral domains of epithelial cells (molecules different), precents diffusion of small molecules and proteins
Adherens junction (function)
joins an actin bundle in one cell to a similar bundle in a neighboring cell
Desmosome (function)
joins the intermediate filaments in one cell to those in a neighbor
Gap junction (function)
allows the passage of small water-soluble ions and molecules
Hemidesmosome (function)
anchors intermediate filaments in a cell to the basal lamina
Interlocking tight junction network
formed by 4-pass transmembrane proteins that make contact across the intercellular space and create a seal (claudin and occludin)
Organization of occludin
has 2 small extracellular loop domains that are hydrophobic, the loops stack very closely on top of each other and across to neighboring domains
Confluence of epithelial cells
As they reach confluence, they become impermeable due to tight junctions and other interactions
Epithelial cells grown on porous membrane filters
Can add things to either apical or basolateral side and can measure passage to the other side of the monolayer to measure transcytosis (tight junctions cause high resistance, electrical resistance)
Transcytosis
mechanism for transporting certain substances across an epithelial sheet that combines receptor-mediated endocytosis and exocytosis
Electron-dense tracer molecules and tight junctions
can be added to either apical or basolateral side, usually tight junctions can be shown to stop the dye from moving to the other side
Placement of adherens junctions
always found next to tight junctions on the lateral surface of cells (towards the basolateral side), sites of attachment to actin cytoskeleton, does not hold cells as close as tight junctions
Ca2+ switch assay
Allow cell juntctions to form on a cell surface and remove calcium so that adherens junctions are separated, addition of antibodies against transmembrane proteins at adherens junctions can be tested for the ability to block formation of the original polarizaed monolayer
Cadherin protein structure
1. Ca2+ binding modules
2. N-terminal modules confers specificity to bind to cadherin on adjacent cell
3. Has a transmembrane domain
4. Highly conserved cytoplasmic domain
5. Exists as a homodimer
6. 5 cadherin repeats
Calcium and cadherins
Has Ca2+ binding sites between each pair of cadherin repeat, so at too low calcium concentration, the homodimer is floppy and at greater Ca2+ levels, the cadherin dimers begin to straighten and then interact with neighbors
Why junction connected to cytoskeleton?
force resistance, otherwise any pulling on proteins (like tight junction proteins) will remove them right out of the plasma membrane
Organization of adherens junction
1. Cadherins cluster to form strong connections
2. α and β catenins link cadherins to actin (also p120)
Cadherins and filopodia
cadherins at the tips of filopodia make first contact with neighboring cells (E-cadherins cause epithelial cells to zipper up next to each other)
E-cadherin
Epithelia
Adherens junction
N-cadherin
Neurons, heart, skeleton muscle, lens, and fibroblasts
Adherens junctions and chemical synapses
Cadherin specificity
The cadherins are similar structurally, but are usually formed on different types of cells or places on cells
Cadherins in neural tube formation
E-cadherin expressed only in the overlying ectodern and N-cadherin only expressed in the neural tube
Cadherin-dependent cell sorting
Labeling two types of cells, either with different cadherins or different levels of one cadherin, shows that there is a sorting out process in which similar cells aggregate with each other
Desmosome (structure)
1. Thicker, stronger, denser than adherins junctions
2. Ca2+ dependent connected to IF
3. Cytoplasmic plaque is formed on the inside of the cell and is made of intracellular anchor proteins
4. IF (keratin) filaments attach to the surface of each plaque
5. Transmembrane adhesion proteins (cadherins) bind to the plaques intracellularly
6. Thicker space at desmosome junction
Desmosome (proteins)
1. Cadherins extracellularly interact with cadherins on the neighboring cell
2. The cytoplasmic tails of desmosomal cadherins interact with plakoglobin (gamma-catenin)
3. Plakoglobin binds to desmoplakin, which binds to the IFs
4. Desmoglein and desmocollin are the main desmosome cadherins
Hemidesmosome (structure)
1. Looks like a half desmosome
2. Connects cell to ECM and links intracellularly to IFs
3. α6β4 integrins
4. Bind to laminin outside and "plaque" proteins on the inside
5. Plaque proteins connect integrin cytoplasmic tails to IFs
Epidermolysis bullosa
severe skin blistering caused by mutations in a component of the hemidesmosome
Anchoring junctions (Cell-Cell)
1. Adherens junction (cadherin, cadherin in neighboring cell, actin)
2. Desmosome (cadherin, desmogleins and desmocollins in neighboring cell, IFs)
Dye experiment to show cell communication (gap junctions)
Inject dye into one epithelial cell and over time it will traverse into neighboring cells, then the whole sheet; shows molecular size limits for passage of different sized dyes
Connexin
protein of 26-40 kD that make up a connexon in a gap junction
Connexon
formed from 6 connexins, can be either homomeric or heteromeric
Gap junctions
formed when 2 connexons overlap, homotypic when homomeric connexon overlap and heterotypic when two different connexons overlap, shuts at high calcium and low pH, opens at low calcium and high pH, channel is large enough to share small metabolites/ions but not proteins
Cell-cell adhesions with junctional adhesion mechanisms
1. Tight junctions-nothing
2. Adherens junctions (adhesion belt)-actin
3. Desmosomes-IF
4. Gap junctions-nothing
Cell matric adhesions with junctional adhesion mechanisms
1. Hemidesmosomes (integrins)-IF
2. Focal adhesions (integrins)-actin
Cell-cell adhesion with nonjunctional adhesion mechanisms
1. Cadherins
2. Ig-like CAMs
3. Integrins
4. Selectins
(2-4=non-cadherin)
Cell-matrix with nonjunctional adhesion mechanism
1. Integral membrane proteoglycan
2. Integrins
Cell Adhesion Molecules (CAMs)
1. Transmembrane proteins
2. Extracellular domain is composed of immunoglobin repeats
NCAM (N=neural)
1. Homophilic, binds other NCAMs
2. Doesn't require calcium
3. Important in fine-tuning adhesive interactions in neural cells during development
VCAM (v=vascular) & ICAM (I=intercellualr)
1. Heterophilic (binds to integrins)
2. Ca2+-dependent (integrins)
3. Inducible expression (not always present on cell surface)
4. Blood cell express (leukocytes, lymphocytes)
5. Required for extravasation
Selectins (function)
interact with carbohydrates on other cell surfaces; essential for binding of leukocytes to endothelial cells during trafficking of cells out of the bloodstream to sites of injury or inflammation
Selectins (structure)
1. Bound to actin inside cell via anchor proteins
2. Selectin comes out of cell with a lectin domain on top of an EGF-like domain at the tip (lectins bind carbohydrates)
Extravasation process
Selectin-carbohydrate interactions mediate rolling (weak adhesion) and integrin-CAM interactions mediate adhesion and extravasation (strong adhesion)