Extracellular Matrix Flashcards
Matrisome
- collection of genes encoding ECM and associated proteins
- Core Matrisome- encodes structural ECM components (collagens, Glycoproteins, Proteoglycans, Elastin and Matrikines)
- Matrisome-Associaed Genes - encode proteins that interact w/ or remodel the ECM
- Secreted factors- growth factors, cytokines,
- ECM regulators - cross-linkers, modifying enzymes, proteases and protease inhibitors
- ECM-affiliated proteins - mucins, lectins, glypicans, syndecans, etc
Collagen Structure
- Repeats of glycine, proline, hydroxyproline
- 3 alpha subunits then form helix
- Hydroxyl groups of pralines and lysine form hydrogen bonds to stabilize helix
- Then must helices packed together- due to glycine
- Pralines provide twist in chain to form helical structure
Osteogenesis Imperfecta
“brittle bone disease”
auto dom; bone fragility, skeletal deformity, short stature, blue sclera, hearing loss, tooth fragility
- Cannot form collagen I fibrils (mutation —> kink in helices—> degraded )
Ehlers-Danlos Syndrome (EDS)
- skin hyper extensibility,joint hyper mobility, easy bruising, cigarette paper scarring
- Mult types…classic, hyper mobility (joint dislocations and pain), vascular (susceptible to ruptures), kyphoscoliosis (hypotonia and joint laxity), arthrochalasia (dislocations, scoliosis, fractures), dermatosparaxis (extreme skin fragility, sagging, hernias)
Scurvy
no ascorbic acid which is required for proline hydroxylation to occur - if no hydroxylation than less stable hydrogen bonds w/in triple helix
Lathyrism
- fragility (in bone or blood) caused by legumes, copper deficiency, BAPN in foods which inhibits lysol oxidases
- AKA inhibits cross linking which is essential for collagen function
Fibrosis
too much collagen; after acute tissue injury; results in lack of organ function and lack of regeneration (esp in hearts, lungs, kidney, liver)
Basement Membrane Components
- Collagen IV - form 2D network (C terminal is NC1 and N terminal is 7S domain)
- Laminins- large glycoproteins that form heterotrimers
Basement Membrane Synthesis (4 steps)
- 1- Laminin LG domain attaches to cell surface receptors
- 2- Laminin globular domains interact w/ ea other forming network
- 3- Other glycoproteins are added
- 4- Whole thing is stabilized by collagen IV
Epidemolysis Bullosa
- blistering disease of skin caused by defective anchoring of epidermis to dermis; severity depends on how deep the mutated structure is
Alport Syndrome
mutation in collagen IV —> glomerular basement membrane affected and cannot maintain filtration barrier —> proteins in urine
Acquired Disease of Basement Membrane
- Diabetes - ILM (special basement membrane that sep retina from vitreous) thickens —> vision loss
- Asthma - thickening of reticular basement membrane in airway
Proteoglycan Structure
- Proteins w/ GAG side chains attached
- Side chains are negatively charged so bind Na+ which brings water with it
- So take up a large volume and resist compression
Pondyloepimetaphyseal dysplasia
- aggrecan mutation —> severe short stature cartilage and bone anomalies; growth plates are cartilage so dysfunctional growth plates —> long bone growth
4 Types of Proteoglycans
- Intracellular - secretory granules
- Cell surface - contribute to sugar coat (glycocalyx), can act as co-receptors go growth factors and can be shed to contribute to ECM
- Pericellular - components of basement membrane; proteolytic products can lead to signaling
- Extracellular - hyalectan, lectican, SLRPs
