L5 Cell Adhesions And Junctional Complexes

Front 1

What the Extracellular Matrix (ECM)types?

Back 1

Basement membrane - epithelial/ endothelial cells;tissue polarity and barrier

Collagens - most abundant; ubiquitous; fibres, tensilestrength

Fibronectin - abundant; fibres; flexibleElastin - fibres, elasticityProteoglycans/Glycosaminoglycans (GAGs) - hydration,packing

Front 2

What roles do they play?

Back 2

All play different but co-operative roles in organismdevelopment, cell adhesion, polarity, proliferation,differentiation, migration

Front 3

What are the sublayers of the basement membrane?

Back 3

• Made up of sublayers:

Basal laminae (nearest epithelial cells) =~120nm thick; major ECM proteins are lamininand collagen IV

Reticular laminae (nearest connective tissue) =connects basal laminae to connective tissue

Front 4

How much of the body weight do collagens make up?

Back 4

Ubiquitous - make up over half of total protein inbody by weight

Front 5

What is the function of collagen?

Back 5

Provides tensile strength and elasticity in to tissues,including bone, skin, cartilage, tendons

Front 6

What is the structure of collagen?

Back 6

3 polypeptide (a) chains each formed of left handedhelix –assemble into right handed helix fibres forstrength

Front 7

What are the different collagens?

Back 7

Different collagens formed by different combinations of a-chains

Type I, II, III = main fibres, flexible

Type I = bone, skin, tendons (90% of all collagen)Type II = cartilage

Type IV = basement membrane

Front 8

What are the fibronectin types?

Back 8

2 different types: soluble (plasma) and insoluble

Front 9

What is fibronectin composed of?

Back 9

Glycoprotein (protein core, sugar side chains)

Front 10

What is fibronectin made by?

Back 10

Primarily made by fibroblasts, epithelial cells and hepatocytes(plasma)

Front 11

What is soluble FN a major component of?

Back 11

Soluble FN is a major component of bloodplasma, secreted as a soluble proteindimer

Front 12

What is fibronectin required for?

Back 12

Required for efficient wound healingresponse - high levels of plasma FN foundat wound sites that act to cluster plateletsand recruit fibroblasts to the site.

Fibroblasts then assemble new matrix toclose the wound to promote woundclosure.FN levels

Front 13

Why might FN levels increase in tumours?

Back 13

FN levels often increased in tumours - proposed to act to promote cell survival,resistance to apoptosis and invasion.

Front 14

What is elastin?

Back 14

Made as tropoelastin soluble monomer (~65kDa)assembles into microfibrils (contains glycoproteins);crosslinked to form insoluble matrix fibres

Front 15

What is the function of elastin?

Back 15

Provides structural integrity totissues (with collagen) andenables reversible changes,extensibility and deformabilityof matrix.

Highly expressed in lungs, skin,major blood vessels

Front 16

What are proteoglycans?

Back 16

Proteoglycans are heavily glycosylatedprotein cores.

Front 17

What do Glycosaminoglycans (GAGs) andProteoglycans do?

Back 17

Form a ‘gel’ that acts to:

- link fibrillar ECM network

- bind soluble factors (eg: cytokines)

- resist pressure and lubricate withintissues under mechanical pressure

- act as signalling molecules

Front 18

How much of the ECM do the proteoglycans fill?

Back 18

Occupy 10% of ECM by weightbut fill larger than 10% volume

Front 19

What do cells form adhesions to?

Back 19

Cells form adhesions to the ECMand/or to each other

Front 20

What are cell adhesions essential to?

Back 20

Cell adhesions are essential toforming and maintaining tissues

Front 21

What are focal adhesions?

Back 21

• Anchor cells to the extracellular matrix

• Large multi-molecular assemblies

• Main receptor family are integrins that act as connectionbetween ECM and actin cytoskeleton

Front 22

What are integrins?

Back 22

Cell-ECM adhesion type

Heterodimeric transmembranereceptors

– a & B subunitsIn mammals

– 8B & 18a subunits = 24different integrinsRecognize motifs in ECM ligands

–ligand specificity relies on bothsubunits

Front 23

What are Hemidesmosomes?

Back 23

Cell-ECM adhesion types

• Epithelial cells

• β4 integrin containing adhesion linking ECM to intermediatefilaments (keratins)

• Intracellular domain of integrins linked to keratin via plectins(anchor proteins)

Front 24

What are Cell-ECM adhesion types:3) Podosomes?

Back 24

• Hematopoietic cells, endothelial cells, bone cells

• Actin core surrounded by integrin containing adhesion ring

–links to F-actin cytoskeleton

• ECM-degrading – required for cells to penetrate/remodelunderlying ECM

Front 25

What are Cell-Cell adhesion types:1) Tight junctions?

Back 25

• Act as a permeability barrier

• Restrict macromolecular transport between cells

• Found in epithelial and endothelial cells

• Important in cell polarity

Front 26

What are Cell-cell adhesion types:2) Adherens junctions?

Back 26

• Maintain cell-cell adhesion in all epithelial and endothelial cells aswell as others

• Cadherins – homotypic adhesion of extracellular domains

• Cadherins in AJ linked to actin via anchor proteins (catenins, actininand vinculin)

Front 27

What are Cell-cell adhesion types:3) Desmosomes?

Back 27

• Maintain cell-cell adhesion (strong mechanical linkers)

• Main components are desmosomal cadherin family members(desmoglein and desmocollin)

• Cadherins are bound to plakophilin and plakoglobin, that in turnbind desmoplakin (and then to intermediate filamentcytoskeleton)

Front 28

What are Cell-cell adhesion types:4) Gap junctions?

Back 28

• Channel forming junctions

• Main components are connexons -connect to form channels and canopen and close

• Allow passage of ions and small2nd messenger molecules betweencells (1kD or less)• Important in heart muscle (signalto contract) and neuronal synapses

Front 29

What does a tight junction do?

Back 29

Seals neighbouring cells together in an epithelialsheet to prevent leakage of molecules between them

Front 30

What does an adherens junction do?

Back 30

Connects actin networks in neighbouring cells

Front 31

What does a desmosome do?

Back 31

Connects intermediate filaments in neighbouring cells

Front 32

What do GAP junctions do?

Back 32

Allow passage of small water soluble ions andmolecules between cells

Front 33

What do hemidesmosomes?

Back 33

Anchors intermediate filaments in a cell to the basallamina

Front 34

What does a focal adhesion do?

Back 34

Anchors actin networks in a cell to the basal lamina

Front 35

What do Podosomes so?

Back 35

Degrades ECM. Actin core with integrin ring.

Front 36

Why must cell-cell and cell-ECM adhesion be tightly co-ordinated during embryonic development?

Back 36

Cell-cell and cell-ECM adhesion must betightly co-ordinated during embryonicdevelopment to allow cells to adhere,divide, migrate and communicate.

Front 37

What helps to dissect the individual roles for proteins in each step of development?

Back 37

• Use of genetically tractable modelsystems (such as mice, zebrafish,Drosophila fruitfly) helps dissect individualroles for proteins in each step ofdevelopment

• Also used for analysis of adhesion indifferent diseases – eg: cancer metastasis,skin blistering, chronic wound healing