Extracellular matrix Flashcards
What is the extracellular matrix?
Network of macromolecules filling spaces between cells. Made of fibrillar and non-fibrillar componants
What collagens are found in connective tissues?
Type I (bone), II (cartilage) III (blood vessels) all fibrillar
Type IV (basement membrane , non-fibrillar)
What multi-adhesive glycoproteins are found in connective tissue?
Fibronectin, Fibrinogen
Laminins (basement membrane)
Which Proteoglycans are found in connective tissue?
Aggrecan
Versican
Decorin
Perlecan (basement membrane)
What does the mutated gene affect to cause Osteogenesis imperfecta?
Type I collagen
What does the mutated gene affect to cause Marfan’s Syndrome?
Fibrillin 1
What does the mutated gene affect to cause Alport’s syndrome?
Type IV collagen alpha 5
What does the mutated gene affect to cause Epidermolysis Bullosa?
Laminin 5, in all 3 chains
What does the mutated gene affect to cause Congenital Muscular Dystrophy?
Laminin 2 Alpha 2 chain
What is an example of disorder of ECM catabolism?
mucopolysaccarides / GAGs inability to be degraded
What is Hurler’s Syndrome?
Mutation which leads to a loss of enzyme L-Alpha-iduronidase.
results in the buildup of large sugar molecules called glycosaminoglycans (AKA GAGs, or mucopolysaccharides) in lysosomes
What category of disorders can be caused by excess ECM deposition? Give 3 examples
Fibrotic disorders
Liver fibrosis - Cirrhosis
Kidney Fibrosis - diabetic nephropathy
Lung fibrosis - iodiopathic pulmonary fibrosis (IPF)
What disorder is Osteoarthiritis an example of?
Disorders due to excess loss of ECM where it is needed for support
Why is there a wide variety of connective tissues?
Different types of collagen with various arrangement coupled with or without different ECM components can create diversity
What are the characteristics of Diabetic nephropathy? Why does it lead to renal failure?
There is an accumulation of extracellular matrix making thick basement membrane, This restricts renal filtration , so can lead to renal failure
What are the characteristics of Alport syndrome?
Mutations in collagen IV resultl in abnormally split GBM which is associated with loss of kidney function and hearing loss.
What do elastic fibres consist of?
Protein elastin core and microfibrils which are rich in protein fibrillin surrounding.
What disorder is caused by mutations in fibrillin 1 protein?
Marfan’s syndrome
skeletal, ocular and cardiovascular system can be affected. Px can be predisposed to aortic ruptures. Arachnodactyly
In the protein Elastin, what are the two segments that alternate along the polypeptide chain?
Hydrophobic regions and alpha helical regions rich in alanine and lysine. many of the lysine side chains are covalently cross linked
What makes ECM proteins multi-adhesive?
Their modular architecture. ie, They are made of protein domains of 50-200 amino acids. Makes them multifunctional and can bind to various components /receptors
What are the structural characteristics of laminins?
Heterortrimeric proteins made of alpha, beta, gamma chains. Form cross shaped molecules. Large proteins
Each chain molecular weight 160-400kDa
How do Laminins act as multi-adhesive proteins?
can interact with receptors Integrins and Dystroglycan.
Can self-associate with basement membrane matrix as well as other matrix components : type IV collagen, Nidogen, proteoglycan
Diseases such as muscular dystrophy, epidermolysis bullosa, congenital muscular dystrophy arise from what?
Absence of alpha 2 chain in laminin 2. Symptoms include hypotonia, weakness and deformities of the joints
Extracellular matrix extra info?
- key functions : physical support, mechanical and physiochemical properties of the tissue, influences the growth, adhesion and differentiation of cells and tissues it interacts with, essential for development tissue function and organgenesis
cells found in connective tissues : fibroblast, macrophage, basal lamina, collagen fibre, mast cell, elastic fibre, capillary, glycosaminoglycans, proteoglycans, glycoproteins
- properties of connective tissues ( tendon and skin = tough and flexible ) ( bone - hard and dense ) ( cartilage = resilient and shock absorbing )
