Actin polymerisation assay


Materials:

Labelled actin, ATP, Polymerisation buffer are stored in aliquots at -80¡C. Please refer to the instruction manual by Cytoskeleton for details and troubleshooting.

1. Preparation of the recombinant proteins

Dia proteins, e. g. ZZ-dia-H6 are purified by Ni-affinity chromatography and stored in aliquots in 50 mM Tris/HCl pH8, 50 mM NaCl, 10% glycerol, 250 mM saccharose at -80C. The concentration should be higher than 1 mg/ml.

2. Depolymerisation of actin

  • add 2 ul 100 mM ATP and 5 ul 100 mM DTT to 1000 ul A buffer (yields G buffer)
  • add 225 ul of G buffer to 5 ul of an pyrene-actin (500 uM aliquots stored at -80C)
  • incubate for 1 h on ice
  • spin for 30 min, 4C, 70k (TLA100.3 rotor), use the special (UZ) reaction tubes

3. Protein in A buffer

  • the protein has to be transfered to a buffer that does not interfere with the polymeristation reaction (no KCl, no Mg2+, no ATP, low buffer concentration)
  • Dia-FH1FH2 shows activity at concentrations higher than 20 nM.

4. Polymerisation

  • the final volume of the reaction mix is 100 ul
  • mix 10 ul of polymerisation starter with 60 ul of A buffer with the protein and load into the cuvette (3 way for fluorometer)
  • start the reaction by adding (and mixing) 30 ul of G-actin in G buffer (final actin concentration is 3 uM)
  • excitation is at 365 nm, fluorescense at 407 nm, read every 12,5 s over 500 s.

Test of actin

Frozen globular actin looses its polymerisation ability. To test the quality of the preparation perform following procedure:
  1. Dissolve actin to 0.2 mg/ml in water. Incubate for 1h at room temperature.
  2. Fill the solution into a fluorometer cuvette and read the fluorescence every minure for 10 min.
  3. Add 1/10 of 10xpolymerisation buffer. Mix.
  4. Read the fluorescence every minute for 30 min.
By incubation at room temperature, actin oligomers are formed. After increasing the Mg concentration and adding K+ ions, their elongation is promoted.

Buffer:

A buffer (1x)

5 mM Tris/HCl pH8
0.2 mM CaCl2

G buffer (1x)

5 mM Tris/HCl pH8
0.2 mM CaCl2
0.2 mM ATP
0.5 mM DTT

ATP stock solution

100 mM, stored at -80¡C

DTT stock solution

100 mM or 1 M, stored at -20¡C

Polymerisation starter (10x)

100 mM Tris/HCl pH 7.5
500 mM KCl
20 mM MgCl2
10 mM ATP