Cytoskeleton
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What are actin filaments made from?
Actin polymer
What are microtubules made of?
Alpha-beta tubulin dimers
What are intermediate filaments made from?
Intermediate filament proteins
What acin polymerises into F-actin?
G-actin
How many other subunits does F-actin contact ?
Three, along the strand and between the two strands
Structure of mysoin
• Myosin (class 2) is a hexameric protein: • Two heavy chains dimerise (via the coiled coil) to form the coiled-coil tail and two globular myosin heads • Each myosin head is composed of a motor domain and a lever. • The lever contains 2 ‘IQ’ motifs (IQxxxRGxxR) • Light chains bind to the IQ motifs – two per lever (two per heavy chain) • Essential light chain (ELC) binds to an IQ motif close to the motor • Regulatory light chain (RLC) binds to the IQ motif close to the coiled coil
Hypertrophic cardiomyopathy (HCM)
Autosomal dominant, typical missense mutations in genes encoding sarcomeric proteins. Left ventricular hypertrophy and myofibrillar disarray
Mutations in MYH7 cause what disease?
HCM
Mutations in MYBPC cause what disease?
HCM
Mutations in loop 1, converter and relay helix likely affect what?
Force generation
Mutations in S2 affect
Interacting heads motif, more ATP usage. Could affect binding of MyBPC
Mutations in non muscle myosin 2A cause these diseases
Blood clotting disorders, deafness and kidney disorder
What does the activation of platelets depends on?
NM2A and actin
What do smooth and non-muscle myosin 2 isoforms form?
10S shutdown state.
What are smooth and noon-muscle myosins activated by?
Phosphorylation of the RLC
Mutations in MYH9 cause what disorders?
Bleeding
Mutations in skeletal muscle actins can cause
Skeletal muscle myopathies
What mutations cause Baraitser-Winter syndrome?
Mutations in beta and gamma actins
Symptoms of Baraitser-Winter syndrome
Changes around the eyes: (congenital ptosis (drooping eyelid), * High-arched eyebrows, * Hypertelorism (increased eye spacing), * Missing tissue around the eye (Ocular colobomata) * Brain malformation - anterior predominant lissencephaly. * May also be short * May also have microcephaly, intellectual disability, seizures and hearing loss
What is critical to forming a highly folded brain?
Neuronal migration
What is important for neuronal migration?
Non muscle actins
Keratin is an example of what type of fibre?
Intermediate
What filaments are required for cell to cell and cell-ECM adhesion?
Intermediate
What happens in the skin epidermis basal layer?
Cells adhere to underlying extracellular matrix through focal adhesions (hemidesmosomes) Cells divide (proliferate) - express K5 and K14 Then migrate upwards to spinous layer: Switch keratin isoform expression to K1 and K10