Muscular Dystrophy Flashcards
Collagen 1 formation
Triple helix formed in the cell driven by the c terminal non collagenous domain (don’t have the motif)
Hydroxylation of the proline and lysine happened often
Cleavage of non collagenous domains
Vitamin C
Co factor for proline hydroxylase
Succinctness is formed from oxogluterate
Types of basal membrane
Stroma unorganised and 3D
Tendon organised and linear
Basal membrane 2D sheet
Type 4. Collagen
Basement membrane only
The non collagenous domains are not cleaved as with type 1
Forms in flat membranes non helical
N terminus forms disulphides bonds between 4 triple helices
C terminus forms end interactions to create hexamers
Combinations of collagen 4
112
345
556
Alports syndrome
Most common form?
Wrong type collagen 4 formation in the kidney as there is only 112 where as 345 is required to protect the kidney basement membranes from the internal pressure as it has more cross links than type 112
Most common is X linked 4a5 never in female
autosomal recessive associated with collagen 4a4 and 4a3
Mutations in…
Early onset
Late onset
Nonsense mutations leading to trucations
Missense leading to conserved cysteine residues affecting crosslinking
Good pastures syndrome
Same as alports but with progressive glomerulonepritis (filter damage)
ACE inhibitors
Reduce onset of alports
Induces vasodilation reducing damage and pressure to the glomerulus
Laminin structure
Three chains
Alpha beta gamma
Chains interact and from a triple helices structure with a globular domain on the C terminus of the alpha chain whilst the N terminus has spacers comprised of EGF repeats at the globular domain
Specific repeating structure forming disulphides bonds at the cross links
Piersons syndrome
Renal disease in eye abnormalities and severe muscular hypontia
Mutation in b2 integrity gene in laminin 11
Epidermolysis bullosa
Laminin 5 mutation cause breaks between the dermal epidermal junction
Loss of 5 causes causes herlitz type
Links structures called hemidesmosomes
Therapies for beta 3 laminin mutations
Transplantation of epidermal cells after retrovirus transduction into the stem cells
Integrins
Heterodimers single transmembrane domain and short cytoplasmic domain but not beta4
Cytoplasmic domain interacts with cytoskeleton such as actin or keratin
Beta 4 integrin deletion
Results in the loss of hemidesmosomes but not cell cell adhesions
Loss of beta 4
Results in absence of alpha 6 subunit
Pyloric atresia
Miss sense mutation in alpha 6 leading to rapid degradation of the integrin autosomal recessive
Eb simplex
Tearing of the epidermis from the basement membrane attachment
Congenital muscular dystrophy
Alpha 2 laminin mutation
Progressive degeneration of muscles
Laminin 211 main muscle BM laminin binding the integrin on the muscle cell surface
Loss of alpha 7 integrin
Results in progressive muscular dystrophy
Duschenne muscular dystrophy
X linked
Mutated dystrophin independent on 71 integrin attachment
Complete loss of dystrophin
Becker MD
Partially functional dystrophin
Dystroglycan glycoprotein complex
Links actin and muscle BM however if both are lost the MD is much worse than the loss of just one
Laminin Dystroglycan binding
Laminin 211 binds glycosylated moieties on dystroglycan however if the Olinked sugars on dystroglycan are removed them laminin cannot bind.
Fukuyama CMD
Autosomal recessive involved in glycosylation of alpha dystroglycan
That doesn’t happen so laminin cannot bind
Disruption of alpha 7 or dystroglycan binding laminin 2
Causes muscle cell apoptosis as akt is activated causing bax to trigger it
Collagen structure definied
Triple helix with
Gly X Y motif
Laminin 1
Embryonic lethal
Laminin 2
Muscular dystrophy
Laminin 5
Epidermolysis bullosa
Integrin b4
Epidermolysis bullosa
B2 integrin
Leukocyte adhesion disorder
