Ex 1 Epitheliam CAMs and Junctional Complexes Flashcards
1
Q
Characteristics of the basement membrane
A
- separates an epithelial layer from its connective tissue support
- approximately 50-80nm thick
- two components: basal lamina, reticular lamina
2
Q
Components of basal lamina
A
- laminin
- fibronectin
- type IV collagen
- entactin
- proteoglycans
3
Q
Laminin
A
- major component
- consists of three chains: alpha, beta, gamma
- has binding sites for interns, type IV collagen, entactin, and proteoglycans
4
Q
Fibronectin
A
- protein made up of two polypeptide chains cross-linked by disulfide bonds
- forms: cellular (produced by fibroblasts, part of extracellular matrix) and plasma (secreted into bloodstream by hepatocytes)
- has binding sites for heparin, interns, collagen, fibrin
5
Q
Type IV collagen
A
- does not form fibrils like type I collagen
- produced by epithelial cells, unlike type I which is secreted by fibroblasts
6
Q
What is the reticular lamina produced by?
A
Connective tissue
7
Q
Two groups of cell adhesion molecules
A
- calcium dependent
- calcium independent
8
Q
Types of calcium dependent CAMs
A
- cadherins
- selectins
9
Q
Types of calcium independent CAMs
A
- integrins
- immunoglobulin superfamily molecules
10
Q
Classes of cadherins
A
Classical vs nonclassical
11
Q
Classical cadherins
A
- major components in calcium-mediated adherin junctions
- typicall form cis and trans homophilic dimers
- include E, N, P-cadherins
12
Q
E-cadherins
A
- type of classical cadherin, calcium dependent
- most common type of cadherins
- form dimers via a HVA binding face (histidine-valine-alanine) which is found at tip of extracellular end of cadherin molecule, calcium ions bind to four extracellular domains a facilitate cis-hemophilic dimers
- loss of e-cadherins is associated with invasive behavior of tumor cells
13
Q
N-cadherins
A
- type of classical cadherin which is calcium dependent
- found in nerve cells
14
Q
P-cadherins
A
- type of classical cadherin which is calcium dependent
- found in placenta
15
Q
Nonclassical cadherins
A
- include desmocollins and desmogleins
- found in desmosomes (macula adherens)
16
Q
Catenins
A
- small proteins that link the cytoplasmic end of a cadherin with cytoplasmic actin
- three forms: beta and gamma (plakoglobin) and alpha
17
Q
Plakoglobin catenins
A
- attached to cytoplasmic end of a cadherin
- beta may also serve as a transcription cofactor
- beta is also attached to alpha catenin (which binds directly to cytoplasmic actin)
18
Q
Selectins
A
- calcium dependent CAM
- bind to carbohydrates therefore they’re lectins
- carb binding site is at carb-recognition domain (CRD) at the extracellular end of the selection
- calcium binding sites are also found near CRD and are required for binding activity (obvi)
- involved in the movement of leukocytes from blood to tissues (extravasation)
19
Q
Classes of selectins
A
- P-selectins: associated with platelets
- E-selectins: associated with activated endothelial cells
- L-selectins: associated with leukocytes
20
Q
Main function of selectins
A
recognize carbohydrates
21
Q
Integrins
A
- calcium independent
- glycoproteins that are mainly involved in cell-extracellular matrix reactions
- bind to extracellular matrix and cytoskeleton
- two subunits: alpha and beta
- interact with RGD sequence in fibronectin and laminin
22
Q
Integrins in hemidesmosomes
A
-link the basal domains of cells to the extracellular matrix via the intracellular monofilaments (intermediate filaments such as keratin)
23
Q
Hemidesmosomes
A
-anchoring junctions that anchor the basal domain of the epithelial cell to the basal lamina
consists of
-cytoplasmic plate associated with intermediate filaments such as keratin
-membrane plaque linking the hemi to the basal lamina via anchoring filaments and integrins
24
Q
Immuoglobulin superfamily molecules
A
- calcium independent CAM
- recognizes integrins
- possess an extracellular segment with one or more folded domains characteristic of immunoglobulins
- N-CAM (neural)
- I-CAM-1 and I-CAM-2
25
N-CAM
- Immunoglobulin superfamily molecule (Ca independent CAM)
- neural adhesion molecule
- mediate both homophilic and heterophilic interactions
26
I- CAM-1 and I-CAM-2
Facilitates transendothelial migration of leukocytes
27
Categories of junctional complexes
- adherens
- occludens
- gap junctions
28
Adherens
- hold cells together
- molecular complexes that anchor cells together and reinforce the physical integrity of cells
- found on basolateral surfaces of epithelial cells
- anchoring junctions characterized by intercellular spaces that are filled with cadherin proteins (such as desmoglein and desmocollins)
29
Desmogleins
- desmoglein 1 and 2 are found in the epidermis
- autoantibodies to desmoglein 1 result in pemphigus foliates
- desmocollins are found in intracellular spaces and are associated with these junctions
30
The cadherin proteins associated with adherents are anchored to...
cytoplasmic plaques containing desmoplakin and plakoglobin
31
Adherin junctional complexes
- zonula adherens are associated with actin microfilaments
- macula adherens are associated with intermediate filaments
- these associations are mediated by interactions with cadherins: desmocollins and desmogleins
32
Occludens
- prevent paracellular transport by preventing molecules from sneaking by cell recognition (occlude)
- establish impermeable barrier between adjacent cells
- maintain concentration differences
33
Gap junctions
- composed of molecular pores that enable cells to rapidly exchange ions and small molecules that help coordinate activities among the cells that make up the tissue
- cardiovascular (heart)
34
Types of junctions
- zonula
| - macula
35
Zonula
- adherens or occludens variety
- travel all the way around cell and link all neighboring cells to central cells
- associatef with intracellular actin
- provide barrier against the paracellular transport pathway whereby solutes and fluids are transported from one side of a barrier to other by passing between cells
36
JAMs
- junctional adhesion molecules
- stabilized by disulfide bonds and form cis-homodimers that facilitate cell adhesion
- member of immunoglobulin superfamily
- associated intracellularly with both afadin and with ZO-1
37
Nectins
- members of immunoglobulin superfamily
- stabilized by disulfide bonds and form cis-homodimers that facilitate cell adhesion
- associated with intracellular molecule afadin
38
Macula
- spot or snap-like junction
- adherens variety and referred to as desmosomes (associated with lateral domains of epithelial cells)
- associated with intracellular intermediate filaments (monofilaments)
- basically adheren junctions
39
Focal adhesion
- spots that anchor the cell to the extracellular matrix via interns
- they differ from desmosomes (macula) in that the intracellular attachment is not to tonofilaments such as keratin but to actin filaments via connecting proteins
- stable or turn over rapidly as cells move
40
Gap junctions
- communicating junction that allow cells to directly communicate
- composed of connections
- closed when calcium ion concentrations are high
- responsible for chemical and electrical coupling
- related pathologies: Charcot-Marie Tooth Neuropathy and Congenital Cataracts
41
Connexons
- make up gap junctions
- composed of six connections, forming a hexagonal structure with hollow center
- facilitate movement of molecules up to 1.2nm in diameter
- often clustered into patches
