Midterm #2: 7-9 pm on Wednesday, November 8, McKenzie 240C

Review Session: 7-9 pm on Thursday, November 2, Lawrence 115

Cytoskeleton and motor proteins

2017-10-30


Conceptual goals

  • Understand that the cytoskeleton give structure and dynamics to the cell
  • Understand how the cytoskeleton is dynamically assembled
  • Understand how motor proteins work and allow movement in cell

Cells are spatially and temporally organized


How do cells get this organized, despite random thermal motion?


Ron Vale, UCSF

What are the "rails?"

  • Actin
  • Microtubules

What are the motors?

  • Kinesin
  • Myosin
  • Dynein

Cells are laced with a cytoskeleton made of actin and microtubules


The cytoskeleton has exquisite 3D structure

The cytoskeleton has exquisite 3D structure

The cytoskeleton:

  • Gives the cell structure and allows cell movement
  • Is built from monomeric subunits
  • Polymerizes in an energy-dependent manner
  • Has a "-" and a "+" end
  • Dynamically breaks down

Actin filaments assemble double-stranded filaments from actin monomers


A conformational change in G-actin leads to polymerization



Holmes (2009) Nature 457:22

Monomeric actin is in equilibrium between G and F forms

F, but not G, catalyzes ATP to ADP hydrolysis (a favorable reaction)


Monomeric actin is in equilibrium between G and F forms

F, but not G, catalyzes ATP to ADP hydrolysis (a favorable reaction)


Other molecules can control polymerization

Polymerizing actin on a slide. 50x real time. Branching occurs when protein Arp2/3 incorporated into chain Credit: Brad Nolen (reseracher at UO)

Microtubules assemble tube structure from $\alpha$ and $\beta$-tubulin


Microtubules dynamically assemble and break down

Credit: Eva Nogales, UC Berkeley

Regulated assembly/dissassembly of cytoskeleton leads to movement.

Regulated assembly/dissassembly of cytoskeleton leads to movement.

The cytoskeleton:

  • Gives the cell structure and allows cell movement
  • Is built from monomeric subunits
  • Polymerizes in an energy-dependent manner
  • Has a "-" and a "+" end
  • Dynamically breaks down

That explains the rails; what about the motors?

Kinesin is an archetypical motor protein

Molecular motors:

  • "Walk" along microtubules and actin
  • Take steps in an energy-dependent fashion
  • Can usually only walk one way down a filament
    • Kinesin walks - to + on microtubules
    • Dynein walks + to - on microtubules
  • Move cargo fast relative to diffusion

Kinesin walks along the microtubule

Kinesin walks like a drunkard

Kinesin goes fast: 5 $\mu m\ s^{-1}$.

For a 1 cm neuron, this means a vesicle can be moved in 5.5 hr.

With just diffusion, this would take roughly 6 days

The cytoskeleton:

  • Gives the cell structure and allows cell movement
  • Is built from monomeric subunits
  • Polymerizes in an energy-dependent manner
  • Has a "-" and a "+" end
  • Dynamically breaks down

Motor proteins

  • Transport materials, move cells, and give muscle contraction
  • "Walk" along microtubules and actin
  • Take steps in an energy-dependent fashion
  • Can usually only walk one way down a filament
  • Move cargo fast relative to diffusion