Actin filaments

• Cell cortex is?

  Actin network on the inner face of the plasma membrane that is capable of dynamic remodeling.

  • Enables cells to crawl/move
  • Enables phagocytosis (by allowing cell to change shape)
  • Cellular constriction during cell division
• Actin-binding proteins do what?

  Regulate the assembly, disassembly and rearrangement of actin networks
• Types of actin-binding proteins: filament nucleating

  • The very beginning of actin filament and the slowest step in the formation of said filament
  • Two types:
  • Arp2/3 complex: Binds to existing filament to create branches. The complex remains at the pointed end of the new branch and has a similar structure to actin monomers.
  • Formins: Generate unbranched filaments (create filaments de novo). They stay associated with the barbed end (fast growing end) to promote rapid elongation of filaments.
• Types of actin-binding proteins: monomer sequestering

  • Bind to actin-ATP monomers to prevent them from being added to the elongating filament.
  • Able to modulate the available monomer pool in certain regions at certain times (i.e., sequester actin monomer pool away)
• Types of actin-binding proteins: End-blocking (capping)

  • Regulate the length of actin filaments
  • Bind at either end of filament
  • Capping at the (+) end prevents rapid growth but dissociation still occurs
  • Capping at the (-) end prevents dissociation although rapid growth may still occur
• Types of actin-binding proteins: monomer polymerizing

  • Binds to actin monomers to promote growth of filaments
  • promotes replacement of ADP (- end associated and dissociate more readily) with ATP (+ end associated)
  • Ex: profilin
  • Binds to same spot as sequestering proteins
• Types of actin-binding proteins: depolymerizing

  • Bind to actin-ADP at the pointed end to promote depolymerization
  • ex. Cofilin
• Types of actin-binding proteins: Cross-linking and bundling

  • Multiple actin binding sites, allowing them to alter the 3D organization of filaments
• Types of actin-binding proteins: filament severing

  • break an existing filament in two
• Types of actin-binding proteins: membrane-binding

  • Helps relay movement forces to plasma membrane
  • Links actin filaments to plasma membrane
  • Enables the plasma membrane to protrude outward (cell locomotion) or inwards (phagocytosis)
• A shift in the concentration or activity of which type(s) of actin binding proteins can cause a shift in the equilibrium between actin monomers and filamentous actin?

  Nucleating proteins, monomer-sequestering proteins, and depolymerizing proteins
• The first step in cell movement is initiated by the creation of a lamellipodium. How is the lamellipodium formed by actin networks?


  1. a stimulus is received at the cell surface
  2. Arp 2/3 complex at the site of stimulation gets activated and binds to the side of an existing filament.
  3. ATP-actin monomers bind to Arp2/3 complex, forming a new branch. Polymerization promoted by profilin
  4. Older filaments get capped at their barbed ends.
  5. Newer filaments continue to grow at the barbed end, pushing the lamellipodium outward. Cofilin promotes disassembly of older capped filaments
• After the lamellipodia is made, how does it grab onto the cell surface?

  Cell grips the surface at adhesion points called focal adhesions. Focal adhesions are where integrin proteins connect to actin. Integrin proteins are transmembrane proteins that mediate the interaction between actin and the surface.
• How is the rest of the cell body hoisted forward after lamellipodia is made and stuck to surface?

  Contraction forces pull the bulk of the cell forward using myosin. Myosin is found near the rear of lamellipodium.
• After the rest of the cell body is hoisted forward, what happens?

  Adhesive contacts to surface break, causing retraction of trailing edge/tail
• Individual actin monomers move down the length of the microfilament from the plus end to the minus end in a process known as treadmilling
• Actin filaments (F-actin) (microfilaments)

  • Actin is the most abundant protein in most cells
  • Filaments are composed to globular subunits (G-actin)

  Involved in cellular motile processes

  • movement of vesicles
  • Phagocytosis
  • Cytokinesis

  Provides structural support

  • shape of cells
  • support for cellular projections
• Structure of actin filaments:

  Polarity

  • + end = barbed end
  • (-) end = pointed end

  Individual G-actin monomers have directionality and are added to the filament in a particular orientation.

  • filaments are a double-stranded helix with both strands orientated in the same direction (to keep polarity)
• Actin assembly and disassembly general

  • ATP-actin is incorporated into the filament. After incorporation, actin hydrolyzes ATP.
  • Although ATP-actin is added to both ends but there is faster addition at the barbed end (+)
  • This is because the barbed and pointed ends have different critical concentrations

  critical concentration is the minimal concentration of available ATP-actin required to elongate

  • Barbed end has a lower critical concentration
• Actin filament assembly/disassembly

  1. Preformed actin filament (seed) in the presence of ATP-actin
  2. At high ATP-actin concentrations, it will be added to both ends
  3. As ATP-actin concentration taper off, the critical concentration of the pointed end is reached first; addition stops at the pointed end
  4. Loss of subunits occurs at the pointed end because ADP-actin dissociates more readily than ATP-actin, but addition continues at the barbed end = steady state (absolute length of filament has not changed)
  5. Relative position of subunits is continually moving (treadmilling)
• Actin assembly/disassembly diagram

  A) seed

  B) high

  C) drops

  D) drops

  E) constant