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44 Cards in this Set

  • Front
  • Back

Intergrin

Facilitates the interaction between cell+ECM

2 types of adhesion molecules Intergrin forms

1) Focal adhesions


2) Hemidesmosomes

Where are tight junctions found

Near the apical surface of epithelium- therefore are important in cell polarity

How do tight junctions maintain polarity

They are at the apical surface and bind to the actin cytoskeleton

Structure of tight junctions

Tight junctions form via homodimerisation.



Therefore claudin+claudin occludin +occludin etc are the basis of tight junctions



Adaptor proteins enable components of tight junctions to anchor to actin and provides structural integrity

Main components of TJ

- Claudin


- Occludin


- JAMs

Location of Adherens Junctions

Sit underneath the TJ

Function of AJ

To maintain cell-cell adhesion

Cadherins in AJ

The predominant type of receptors in AJ + desmosomes



Adhesion is homotypic (homodimerisation)



In AJ the type of cadherins used is E-cadherin



Are also ca2+ dependent

Structure of AJ

Cadherins in AJ link to actin via anchor proteins



Adaptor proteins are catinins, actinin, vinculin



Adaptor proteins are important in connecting receptor to F-actin and also proved structural integrity

Desomosome

Are important in maintaining cell to cell adhesion

Cadherins in desmosomes

Main component is desmosomal cadherins - desmoglein and desmocollin



Cadherins are bound to plakophillin and plakoglobin adaptor proteins.



Adaptor proteins anchor desmosome to the intermediary filaments of cytoskeleton

Focal Adhesions

Anchor cells to ECM.



Main receptor family are intergrins that act as connection between ECM and cytoskeleton

Structure of Focal adhesions

Hetrodimeric transmembrane receptors with alpha and beta subunits



There are many types of subunits and different interaction between different subunits mean that there are 24 different intergrins

Basement Membrane

Is a thin ECM tissue which separates the epithelium and the endothelium from the underlying connective tissue.




Consists of two sublayers:


Basal Laminae - nearest to the epithelial cells (laminin + collagen IV)


Reticular laminae - nearest to connective tissue

Molecular structure of Laminins

Cross shaped, trimeric glycoprotein of polypeptides alpha, beta and gamma




Different combinations of alpha, beta and gamma chain = 15 types of chains

Size of Laminins

900 kDa

Laminin

A fibrous protein present in the basal lamina of the epithelium and is essential for structural integrity.

Laminin contains binding domains for...

Collagen IV, Nidogen, Heparin, Heparin sulphate, Perlecan, cell binding

Structural arrangement of laminins

'short' arms of cross structure bind other laminins to create sheet

Collagen

Ubiquitous structure protein which provides tensile strength and elasticity in: tendons, cartilage, bone

Molecular structure of collagen

3 polypeptide alpha chains of a left-handed helix form right handed fibres




Different forms of collage is created by different combinations of alpha chains

Type I collagen

Found in bone, skin, tendons (90% of all collagen)

Type II collagen

Found in cartilage

Type IV collagen

found in the basement membrane

collagen synthesis

Synthesised on mRNA @ER


protein into ER lumen and post-translation modification


Soluble procollagen moved to golgi apparatus


@golgi packaged into secretory vesicles


Procollagen processed outside the cell and is assembled into fibrils

Fibrosis

@lungs, liver, skin


Excessive deposition of Collagen I or III by fibroblasts


Results in loss of tissue function: lungs loss of oxygen exchange

Scurvy

Lack of vitamin C = formation of unstable procollagen

Brittle bone disease

Mutations in genes encoding type I collagen and results in poorly formed collagen helices

Fibronectin

Is a glycoprotein of the ECM and is most abundant in heart lungs and liver.


Can be soluble/ insoluble

Soluble Fibronectin

a major component of blood plasma




Required for wound healing. Plasma FN @ wound cluster platelets and recruit fibroblasts to the site

Insoluble fibronectin

assembles into a fibrillar ECM at the cell membrane. Can bind to collagens, fibrin and proteoglycans.

Function of fibroblasts

Essential for mammalian development and embryogenesis and cell migration.


Also for wound healing

Tropoelastin

Precursor of elastin:


- soluble monomer


- assembles into microfibrils


- cross links to form insoluble matrix fibres

Elastin

Provides structural integrity and flexibility to tissues with collagen




Highly expressed in lungs, skin, major blood vessels

Proteoglycans

Heavily glycosylated protein core and from a gel which acts to link fibrillar ECM network, resist pressure and act as signalling molecules

Hyaluronan

The main GAG in connective tissue. Form the back bone for assembly of other GAGs




Major component of synovial fluid and vitreous humour

Matrix metalloproteinases

Degrade matrix components + depend on ca2+ and zn2+




Inhibited by tissue inhibitors of metalloproteinases

Serine proteases

Degrade matrix components via highly reactive serine residues




Acts via cleavage of peptide bonds in proteins


Have a highly reactive seriene @ active site




Inhibited by serine protease inhibitors

Focal adhesions in migrating cells

When a cell is migrating new adhesions assemble at the front and old disassemble at the rear

Hemi-desmosomes

Integrin containing adhesion linking ECM to intermediate filaments




Intracellular domains of integrin linked to keratin via anchor proteins plectins




Hemi-desmosome and focal adhesions occupy distinct areas of the cell membrane

GAP junctions

Channel forming junctions main component are connexins




Allow passage of small ions and 2nd messenger molecules between cells

Connexins

Are the main component of the GAP junctions.


They are transmembrane proteins that connect to form channels and can open and close

Pemphigus Vulgaris

Antibodies against desmogleins in desmosomes.




Leads to separation of keratinocytes and from basal layer if the epidermis




Causes skin blistering