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Cytoskeletal Elements, 2.Attachment of cell: Focal adhesion has integrin…

- - - - GTP being bound makes filaments more stable. Hydrolysis of GTP causes rapid depolymerization via curve.
    - - Vincristin/vinblastin treats cancer via inhibiting MT assembly
      - Taxol (paclitaxel) treat breast cancer and stabilize MT
      - Colchicine treats gout and it depolymerize MT
  - - - Results in aggregate tangles
      - Promotes MT disassembly
    - - Protein: Kinesin (plus end) moves towards cell periphery. Anterograde trafficking.
  - - - Axonemal dynein moves flagella by causing MT bending
    - - Accessory proteins: Outer and inner dynein arms w/ nexin in btwn the inner arms.
    - - Disease: Kartagener syndrome or situs inversus totalis bc primary cilium involved in mechanosensors, sense directionality.
- - - - Actin Toxins
        
        Toxin: Phalloidin binds to F-actin and stabilizes it, preventing depolymerization.
        
        Toxin: Latrunculins disrupts by binding G-actin and preventing incorporation
        
        Toxin: Cytochalasin binds plus end. Results in depolymerization bc other side depolymerize
      - Cell Motility
        
        Protrusion: Lamellipodia is pushed at the front of cell
        
        Protein: Rac controls lamellipodia extension via Arp2/3
        
        Rho A g protein activates ROCK which activates LIM kinase, phosphorylating cofilin and inactivating it..
        
        Protein: Cofilin- twists actin, promoting depolymerization behind leading edge. Phospho-cofilin is inactive form controlled by Rho.
        
        Protein: Profilin v. Thymosin counter each other. Profilin delivers Atp-G-actin to filament. Thymosin prevents G-actin incorporation. Will be at lamellipodia
        
        Contraction: Controlled by Rho at the back edge where it causes contractions via myosin contractile machinery
    - - Protein: Fimbrin-crosslink btwn actin fibers to make bundles
- - - - Weak contacts of epithelia lead to blistering and mechanical force trauma.
  - - - Fx: Nuclear support and DNA protection. DNA may bind lamins for support
    - - Myopathies - degen of striated muscles
        
        Disease: Emery Dreifuss muscular dystrophy
        
        Mutation in lamin A or emerin (EMD gene)
        
        Sx: Deep tendon reflex absent and muscle weakness
        
        Sx: Flexion contractures. and shortening of calcaneal tendon
        
        Abnormal cardiac rhthyms.
      - Lipodystrophies - degen of adipose
        
        Dunnigan's lipodystrophy
      - Neuropathies - degen of peripheral nerve
        
        Disease: Charcot Marie tooth disorder type 2B
        
        Mutation in Lamin A or emerin
        
        Type 2A relates with mitochondrial DNA w/ mitofusin 2 being mutated.
        
        Onset is 1st to 2nd decade of life
        
        Sx: Distal muscle weakness and atrophy.
      - Disease: Hutchison-Gilford progeria
        
        Mutation in LMNA
        
        Premature aging in infants