ECM

Question 1

Definition of ECM

Answer 1

insoluble part of the substance surrounding the cell, complex network of proteins and carbs, fibrillar and non-fibrillar

Question 2

Function of ECM

Answer 2

physical support, mechanical and physiochemical properties, influence growth adhesion and differentiation, development tissue function and organogenesis.

Question 3

relationship between ECM and connective tissue

Answer 3

high proportion of ECM in connective tissue surrounding very few cells cells don’t touch, in comparison to epithelium in which the cells are very tightly packed. basal membrane separate epithelial from connective tissue

Question 4

describe scurvy

Answer 4

lack of vitamin C essential for hydroxylation of proline and lysine which allow collagen fibres to form hydrogen bonds

Question 5

What is caused by a lack of collagen

Answer 5

stretchy skin

Question 6

describe marfan’s syndrome

Answer 6

mutation in fibrillin 1 - tall, elastic fibres: skeletal, ocular, and cardiovascular system, predisposed to aortic ruptures. differs depending on the mutation, many different mutations.

Question 7

what caused osteogenesis imperfecta

Answer 7

type 1 collagen

Question 8

describe Alport’s syndrome

Answer 8

Type iv collagen (a5) filtration issue and lack of kidney function, affects ears.

Question 9

describe epidermolysis bullosa

Answer 9

Laminin 5 in all chains

Question 10

what causes congenital muscular dystrophy

Answer 10

Laminin 2 a2

Question 11

gene mutations affecting ECM catabolism

Answer 11

Hurler’s syndrome - L-a-iduronidase

mucopolysaccharidoses - inability to degrade GAGs

Question 12

fibrotic disorders

Answer 12

liver fibrosis - cirrhosis
kidney fibrosis - diabetic nephropathy
lung fibrosis - silicosis

Question 13

what is caused by excessive loss of ECM

Answer 13

osteoarthritis

ehler’s danlos syndrome - collagen cant hold without tensile strength

Question 14

major components of ECM

Answer 14

Collagen 
elastin 
integrin 
multi - adhesive glycoproteins 
proteoglycans

Question 15

collagen characteristics

Answer 15

fibrous
42 genes 27 types
composed of alpha polypeptides form fibrils
three polypeptided aggregate forming a triple helix rope like structure with the same or different alpha chains type II and III only one chain type
each third AA is glycine, so that it fits in structurally
fibrils line up in parallel and form fibres
Propeptides, non collagenous domains at C and N, removed when leave Golgi
joined by covalent bonds
vit C and Fe2+ hydroxylates lysine and proline allowing more hydrogen bonds to form adding to the strength.
lysine and hydroxylysine modified for covalent bonds
fibril associated collagens
type IV - network forming collagen
sheet like network
have propeptides, aggregate together.

Question 16

collagen function

Answer 16

tensile strength, resistant to stretching, skin bone and cornea perpendicular - resist stretch in all directions, tendon parallel - tensile strength in one direction

Question 17

elastin characteristics

Answer 17

elastin and microfibrils
globular monomers
mix of hydrophobic and alpha helical regions - alanine and lysine
lysine side chains - covalently cross linked
Elastin core and microfibrils (rich in fibrillin)
Allow tissues to stretch

Question 18

elastin function

Answer 18

allow stretching. skin, blood vessels dilate, lungs inflate and deflate

Question 19

integrin

Answer 19

transmembrane receptor - bind to ECM and cytoskeleton - proteoglycans are attached to cytoskeleton
bind to laminin

Question 20

hyaluronan

Answer 20

(gag chain) - no core protein, cube each side same size as collagen fibre, synthesised at cell surface, unsulfated.
proteoglycan

Question 21

decorin

Answer 21

associated with collagen, regulates the size of the fibres and makes sure that they are all regular. 1 gag chain, dermatan sulphate
proteoglycan

Question 22

aggrecan

Answer 22

-100 gag chains, - cartilage. hyaline cartilage aggrecan bind to hyaluronan (Link protein), aggrecan v. negative with sulfate and carboxylate groups attract anions and so water - resistant to compression. in oesteoarthritus the aggrecan fragments cant retain as much water - inflammation, rubbing of bones and formation of new bones.
proteoglycan

Question 23

how does gag chain link to proteoglycan

Answer 23

gag chain always bind to proteoglycan vua serine and a specific heterosaccharide.

Question 24

biosynthesis of collagen

Answer 24

post translational modifications - procollagen is secreted from the cell in a vesicle, and the propeptides are cleaved
hydroxylation of lysine and proline, modifications of lysine and hydroxylysine for covalent bonds

Question 25

assembly of collagen

Answer 25

alpha chains - protein synthesis
hydroxylation and glycosylation
triple helix form from three alpha chains - fibril
propeptides cleaved
fibril line in parallel, covalent and hydrogen bonds mean they bond and form collagen fibres

Question 26

definition of basement membrane

Answer 26

Flexible, thin mat of ECM underlying epithelial sheets and tubes

Question 27

function of basement membrane

Answer 27

Separates the connective tissue from the epithelial tissue

Question 28

proteins in BM

Answer 28

large, multi-adhesive and multifunctional - due to the many domains

Question 29

laminin

Answer 29

glycoprotein
3 chain, alpha beta gamma, alpha biggest bind integrin dystroglycan and perlecan, gamma self adhesive and nidrogen and beta self assembly
globular domains
cross shape
absence of alpha 2 chain leads to muscular dystrophy - hypotonia, weakness, deformaties of joints

Question 30

fribronectin

Answer 30

V shaped - bind to collagen and cell receptors
glycoprotein
splicing makes variations
disulphide at c terminal
because it can interact with cells it regulates cell adhesion.
RGD - integrin recognise motif and so this is where they bind
make mechanical continuum with cytoskeleton (actin)

Question 31

proteoglycans in BM

Answer 31

core protein with GAG chains

perlecan is the one in the basement membrane

Question 32

collagen in BM

Answer 32

IV

till has propeptides - join together forming matrix