L2: Microfilaments (actin and myosin) Flashcards
CS is crucial in…
- General cell processes
- Migration of cancer cells (metastasis)
- Normal embryonic development
- Tau protein tangles; Alzheimer’s (CS big target for drug development)
Basic structure, role and width for each type of filament
- Actin
2 strands form a microfilament. 7-9nm width. Provide structural support, some types of cell motility - Microtubules
9+2 alpha, beta-tubulin arrangement. 25nm width. Provide support and involved in cell polarity. - IM filaments
Rope-like, 10nm width. Provide support for nuclear membrane and involve in cell adhesion.
Assembly and disassembly of actin filament (+ treadmilling)
- ATP-G actin binds to end, converted to F actin, hydrolyses to ADP, Pi
- (-) end has actin binding site
- Cc occurs at an end when assembly and disassembly rate are equal; (+) 0.12microM, (-) 0.6microM
- Treadmills when travelling at constant length (below Cc (-), above Cc (+))
Actin binding proteins
- Profilin (phosph. ADP-G actin)
- Cofilin (aids disassembly at (-))
- Thymosin beta-4 (forms deposit of ATP-G actin for when needed)
- Capping proteins (pause process)
Types of capping protein (+ vs -)
(+) CapZ, (-) Tropomodulin
Further capping proteins
- Formin
- ARP2/3
- Phalloidin
Crosslinking proteins and their applications
- Fimbrin (microvilli)
- Spectrin (cell cortex)
- Filamin (filopodia)
- Dystrophin (muscle cell cortex)
Duchenne muscular dystrophy
- The dystrophin gene (on the X chromosome), is defective in Duchenne muscular dystrophy, is an adapter protein that binds to cytoskeletal components such as actin and to the cell-adhesion molecule dystroglycan.
- Dystrophin is part of the muscle cortical cytoskeleton and mutations result in impaired muscle function and shortened lifespan
About myosin (basic action, uses)
- Uses energy drived form ATP-hydrolysis to ‘walk’ along actin filament
- Generates contraction, cellular transport
Myosin Structure
- Motor subunit (1 or 2 heavy chains) with head and tail domain
- Several light chains
- Head domain constant between types, tail varies
Function of domains of myosin
- Head: interact with actin, bind and hydrolyse ATP -> generates force to move
- Tail: specify cellular component
Familial hypertrophic cardiomyopathy
- Caused by mutation in myosin II
- Enlargement of heart
- Sudden death
Myosin movement
- power stroke
- step size generally depends on length of neck region
4 contrasts between myosin V and II
- Myosin V proteins have a longer neck than Myosin II
- Myosin II proteins can assemble into bipolar filaments involved in contractile functions
- Myosin V also has a globular cargo binding domain at its tail
- Myosin V has two ‘legs’ so able to move hand-over-hand
Explain the adaptability of myosin II
Whilst hundred of myosin heads may be involved in contraction, but at any one time some may be bound only transiently and some properly bound in order to move the filament. Able to move quickly with light loads but adapt force for heavier loads.
Short duty cycle and cooperative action between myosin II proteins.
