extracellular matrix Flashcards
what is the ECM?
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
what are the protein components of the ECM?
collagens perlecan laminin fibronectin enactin
what are collagens?
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
what is the function of collagens in the ECM?
gives a high tensile strength
what is the structure of fibril forming collagens?
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
what is the structure of sheet forming collagen?
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
what is perlecan?
a modular proteoglycan
what is the structure of perlecan?
protein-polysaccharide complex with a thin core protein attached to glycosaminoglycans
have a repeating disaccharide structure
binds type IV collagen to enactin
what do negatively charged glycosaminoglycans attract?
cations which in turn attract water
forms a porous hydrated gel
what are the most common glycosaminoglycans?
chondroitin sulphate and keratin sulphate
what links glycosaminoglycans?
hyaluronic acid
what is the structure of laminins?
alpha, beta and gamma polypeptide chains
which interact to form a network of laminins
forms a second lattice interwoven with type IV collagen
what is the role of enactin in the ECM?
cross links laminin, perlecan and type IV collagen
important for membrane stabilisation especially during late embryogenesis
what is the structure and role of fibronectin?
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
what occurs when fibronectin binds to integrins?
the actin cytoskeleton is reorganised
what part of fibronectin is recognised by integrins?
the RGD motif
what are the 3 amino acids that make up the RGD motif?
arginine
glycine
aspartate
what are hemidesmosomes?
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
what degrades materials in the ECM?
matrix metalloproteinases
how does cell migration occur through interaction with the ECM?
focal adhesion points are stimulated
enhances the cell adhesion to the ECM
generates the force needed to propel the cell during migration
what is the basal lamina?
a 40-120nm basement membrane
specialised form of ECM
separates internal and external linings of the organ
what is osteogenesis imperfecta?
brittle bone disease
what are the causes of osteogenesis imperfecta?
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
what are the most common mutations involved in osteogenesis imperfecta?
glycine substitutions in the helical domain
glycine is responsible for the delay of helical formation increasing the access for modification enzymes
what do mutations in the LAMA2 gene result in?
muscular dystrophy
