Lecture 20: Motors, Actin, Cell Motility

MT-Associated Non-Motor Proteins

• Control MT organization in cytosol (e.g. Tau protein in neurons)

• Defective Tau protein → neurofibrillary tangles → Alzheimer’s disease (right image, top)

  • Defect in Tau biology associated with

    Alzheimer’s disease, as well as other forms of

    neurodegenerative disorder (tauopathies)

Mt-associated motor proteins

uses ATP to generate force, can move material along MT track, can generate sliding force between MTs, two types:

• Kinesin: plus end-directed

• Dynein: minus end-directed

Motor proteins and movement

1. ATP binding to the leading head (the one on the right) induces a conformational change that swings the trailing head (the one on the

   left) 180º towards the (+) end of the microtubule. This is the force-generating step

2. The new leading head quickly binds to a tubulin subunit and releases its ADP, moving the kinesin’s cargo forward

3. In the trailing head, ATP is hydrolyzed to ADP, which leads to detachment from the microtubule

4. ATP binds to the leading head to repeat the reaction cycle

Zebrafish embryos

survival mechanism: re-distribute melanin granules for camouflage

• kinesin: dispenses melanin granules outwards in the dark, causing darkly coloured embryo

• dynein: dispenses melanin granules towards the centered, causing lightly coloured embryo

Microtubule-organizing center (MTOC)

• Only found in eukaryotic cells

• Central site of MT assembly

  • motor MAPs generate sliding force between MTs

• The two most important types of MTOCs are 1) the basal bodies associated with cilia and flagella and 2) the centrosome associated with spindle formation

Cytoskeleton

Intermediate filaments

• Intermediate-size (10-12 nm diameter)

• Exclusive to multicellular animal cells

• Provide structural support and mechanical strength

• Stable in comparison to MTs or microfilaments

• Arrangement of fibrous α-helical proteins

  • keratins are stained red, lamins are stained blue

• Not polar (i.e. no ‘plus’ and ‘minus’ ends). For that reason, IFs
  are not used for transport.