Cell adhesion and the extra cellular matrix

Question 1

What is connective tissue extra cellular matrix made out of?

Answer 1

Fibrillar proteins (collagen, elastin, fibronectin and laminin) and hydrated gel of GAGs (these are polysaccaharides called glycosaminoglycans)

Question 2

What are the cells of connective tissue?

Answer 2

Fibroblasts, myofibroblasts, blood derived (mast cells, plasma cells and macrophages), chondroblasts, osteocytes and adipocytes

Question 3

Funtion of fibroblasts?

Answer 3

Synthesis and secrete collagen, elastin and proteoglycans

Question 4

Describe collagen synthesis

Answer 4

Translation of collagen (glycosylation) occurs in the ER of fibroblasts.
Triple helix procollagen formed from single chain pre-procollagen (vit C needed.)
Procollagen travels to Golgi - packed into secretory vesicals and exocytosed. It is then trimmed into tropocollagen and crosslinked to form a fibril.

Question 5

What makes collagen secretion special?

Answer 5

Collagen is packaged into specialised vesicals which are much larger than normal.

Question 6

Where does production of a collagen fibril occur?

Answer 6

In a membrane tube called a fibripositor

Question 7

Where is elastin made?

Answer 7

In fibroblasts, smooth muscle cells and chondroblasts.

Question 8

Describe the some features of elastin?

Answer 8

It contains hydrophobic amino acids which gives it its default recoil position.
Cross links form between elastins meaning connective tissue has the ability to contract

Question 9

What are proteoglycans made out of?

Answer 9

Polysaccharides called glycosaminoglycans and protiens

Question 10

What do proteoglycans provide?

Answer 10

Matrix support, cushioning and hydration. It has a glue like function and connects proteins of the ECM and links proteins between the ECM and the cell surface.

Question 11

Describe the structure of Glycosaminoglycans?

Answer 11

Long chains on repeating disaccharides (polysaccharides), negativly charged and absorb lots of water meaning they are highly hydrated.

Question 12

Describe linking between the ECM to intracellular cytoskeleton

Answer 12

Actin from the cytoskeleton binds to an adaptor protein which is bound to an integrin protein. Collagen/proteoglycans bind to fibronectin (adapter protein) which links to the integrin protein.
These binding properties cause a structural link.

Question 13

Describe the functions of a myofibroblast

Answer 13

It is bi-functional. It secretes collagen and also synthesises actin, myosin and desmin (muscle cells). It is differentiated from a fibroblast under mechanical tension.

Question 14

How are myofibroblasts involved in tissue damage?

Answer 14

They proliferate, secrete collagen, consolidate the damaged tissue (forming a fibrous scar), they contract to reduce the side of the damages area and express focal adhesions and smooth muscle actin.

Question 15

Describe a basic feature of a mast cell

Answer 15

Contains granules that include heparin and histamine

Question 16

Describe a basic feature of a Plasma cell

Answer 16

Production of antibodies via a secretory pathway

Question 17

Describe a basic feature of a macrophage

Answer 17

They ingest by phagocytosis and present antigens

Question 18

Describe the functions of adipocytes

Answer 18

Insulation, packing and energy stores

Question 19

What is Leptin?

Answer 19

The hormone that tells your body to stop eating

Question 20

Describe the features of tight junctions

Answer 20

Fence of membrane lipids and proteins to separate membrane domains.
The control passage of substances between cells
They are able to link to actin in the cytoskeleton

Question 21

What are the two main proteins that make up tight junctions?

Answer 21

Claudins and occludins

Question 22

Describe some of the features of adherens junctions

Answer 22

Anchors actin filaments at the membrane.

Question 23

What are cadherins?

Answer 23

A type transmembrane protein involved in adherens junctions

Question 24

Name the different types of cadherins

Answer 24

E-cadherin (epithelia)
N-cadherin (neurons and heart muscle)
P-cadherin (placenta and epidermis)
VE-cadherin (endothelium)

Question 25

Describe the function of desmosomes

Answer 25

Provide links between strong intermediate filaments in adjacent cells

Question 26

Describe the function of gap junctions

Answer 26

The allow for communication,
provide a hydrophobic channel,
allow small molecules to pass through cells.

Question 27

What proteins make up gap junctions?

Answer 27

connectin

Question 28

Describe the function of focal adhesions

Answer 28

Link the ECM through transmembrane proteins (integrins) with the cytoskeleton.
Act as signalling platforms
Link to fibronectin

Question 29

Describe the function of hemi-desmosomes

Answer 29

Link the ECM through transmembrane proteins to the cytoskeleton. Provide stability by linking epithelial cells to BM, they achieve this by binding to laminin in the BM.

Question 30

Describe the molecular defect in Duchenne Muscular Dystrophy

Answer 30

Gene mutation results in the absence of dystrophin (adaptor protein) due to premature stop signal (termination of translation).
It results in damage to muscle fibres due to muscle tearing. This gives symptoms of muscle weakness and wasting.

Question 31

Outline the significance of cell adhesion and ECM interactions in the spread of cancer.

Answer 31

Carcinoma cells transition from epithelial to mesenchymal and then there is a reduction in cadherin production.
Microinvasion into the ECM is aided by invadipodia and the BM is breached.
Cells secretion metalloproteases (MMPs) which breakdown proteins in the ECM.
Invading tumor cells express integrins which promotes interaction with ECM.
Motility of cancer cells increases and decrease of E-cadherins.
Angiogenesis factors promote vascularisation, cells eneter blood vessels and lymphatic vessels.
Metastasis.