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
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2
Q

Components of basal lamina

A
  • laminin
  • fibronectin
  • type IV collagen
  • entactin
  • proteoglycans
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3
Q

Laminin

A
  • major component
  • consists of three chains: alpha, beta, gamma
  • has binding sites for interns, type IV collagen, entactin, and proteoglycans
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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
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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

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6
Q

What is the reticular lamina produced by?

A

Connective tissue

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7
Q

Two groups of cell adhesion molecules

A
  • calcium dependent

- calcium independent

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8
Q

Types of calcium dependent CAMs

A
  • cadherins

- selectins

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9
Q

Types of calcium independent CAMs

A
  • integrins

- immunoglobulin superfamily molecules

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10
Q

Classes of cadherins

A

Classical vs nonclassical

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11
Q

Classical cadherins

A
  • major components in calcium-mediated adherin junctions
  • typicall form cis and trans homophilic dimers
  • include E, N, P-cadherins
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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
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13
Q

N-cadherins

A
  • type of classical cadherin which is calcium dependent

- found in nerve cells

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14
Q

P-cadherins

A
  • type of classical cadherin which is calcium dependent

- found in placenta

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15
Q

Nonclassical cadherins

A
  • include desmocollins and desmogleins

- found in desmosomes (macula adherens)

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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
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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
Q

N-CAM

A
  • Immunoglobulin superfamily molecule (Ca independent CAM)
  • neural adhesion molecule
  • mediate both homophilic and heterophilic interactions
26
Q

I- CAM-1 and I-CAM-2

A

Facilitates transendothelial migration of leukocytes

27
Q

Categories of junctional complexes

A
  • adherens
  • occludens
  • gap junctions
28
Q

Adherens

A
  • 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
Q

Desmogleins

A
  • 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
Q

The cadherin proteins associated with adherents are anchored to…

A

cytoplasmic plaques containing desmoplakin and plakoglobin

31
Q

Adherin junctional complexes

A
  • 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
Q

Occludens

A
  • prevent paracellular transport by preventing molecules from sneaking by cell recognition (occlude)
  • establish impermeable barrier between adjacent cells
  • maintain concentration differences
33
Q

Gap junctions

A
  • 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
Q

Types of junctions

A
  • zonula

- macula

35
Q

Zonula

A
  • 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
Q

JAMs

A
  • 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
Q

Nectins

A
  • members of immunoglobulin superfamily
  • stabilized by disulfide bonds and form cis-homodimers that facilitate cell adhesion
  • associated with intracellular molecule afadin
38
Q

Macula

A
  • 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
Q

Focal adhesion

A
  • 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
Q

Gap junctions

A
  • 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
Q

Connexons

A
  • 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