extracellular matrix

Question 1

what is the ECM?

Answer 1

a gel-like matrix composed of water, proteins and polysaccharides
each tissue has a unique ECM composition and topology
generated during tissue development and is dynamic

Question 2

what are the protein components of the ECM?

Answer 2

collagens 
perlecan 
laminin 
fibronectin 
enactin

Question 3

what are collagens?

Answer 3

a fibril glycoprotein found in ECM
most abundant protein in the human body
all collagens form a trimer of polypeptide chains wound around each other forming alpha helices

Question 4

what is the function of collagens in the ECM?

Answer 4

gives a high tensile strength

Question 5

what is the structure of fibril forming collagens?

Answer 5

type II and III can form homotrimers
type I can form homodimers
consist of 3 polyproline II helices in a triple helix
stabilised by glycine every third amino acid residue
high concentration of proline and hydroxyproline

Question 6

what is the structure of sheet forming collagen?

Answer 6

composed of type IV collagen
have imperfections in the glycine, proline and hydroxyproline allowing the collagen to be flexible
imperfections can occur up to 26 times
interactions between collagen molecule gives stability to the network

Question 7

what is perlecan?

Answer 7

a modular proteoglycan

Question 8

what is the structure of perlecan?

Answer 8

protein-polysaccharide complex with a thin core protein attached to glycosaminoglycans
have a repeating disaccharide structure
binds type IV collagen to enactin

Question 9

what do negatively charged glycosaminoglycans attract?

Answer 9

cations which in turn attract water

forms a porous hydrated gel

Question 10

what are the most common glycosaminoglycans?

Answer 10

chondroitin sulphate and keratin sulphate

Question 11

what links glycosaminoglycans?

Answer 11

hyaluronic acid

Question 12

what is the structure of laminins?

Answer 12

alpha, beta and gamma polypeptide chains
which interact to form a network of laminins
forms a second lattice interwoven with type IV collagen

Question 13

what is the role of enactin in the ECM?

Answer 13

cross links laminin, perlecan and type IV collagen

important for membrane stabilisation especially during late embryogenesis

Question 14

what is the structure and role of fibronectin?

Answer 14

linear array of distinct polypeptides giving it a modular structure
contains RGD loop
it binds to collagen and cell surface integrins
secreted by cells in unfolded form allowing them to form dimers

Question 15

what occurs when fibronectin binds to integrins?

Answer 15

the actin cytoskeleton is reorganised

Question 16

what part of fibronectin is recognised by integrins?

Answer 16

the RGD motif

Question 17

what are the 3 amino acids that make up the RGD motif?

Answer 17

arginine
glycine
aspartate

Question 18

what are hemidesmosomes?

Answer 18

basal attachments of epithelial cells to the basement membrane in vivo
anchors cellular filaments to the ECM via integrin
appear to be restricted to epithelial cells

Question 19

what degrades materials in the ECM?

Answer 19

matrix metalloproteinases

Question 20

how does cell migration occur through interaction with the ECM?

Answer 20

focal adhesion points are stimulated
enhances the cell adhesion to the ECM
generates the force needed to propel the cell during migration

Question 21

what is the basal lamina?

Answer 21

a 40-120nm basement membrane
specialised form of ECM
separates internal and external linings of the organ

Question 22

what is osteogenesis imperfecta?

Answer 22

brittle bone disease

Question 23

what are the causes of osteogenesis imperfecta?

Answer 23

primary defects in type I collagen
can be a result of:
insufficient quantity of collagen
abnormal post-translational modification
incorrect folding
mutations in genes that encode for collagen

Question 24

what are the most common mutations involved in osteogenesis imperfecta?

Answer 24

glycine substitutions in the helical domain

glycine is responsible for the delay of helical formation increasing the access for modification enzymes

Question 25

what do mutations in the LAMA2 gene result in?

Answer 25

muscular dystrophy