Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

904 Chapter 16: The Cytoskeleton
soluble subunits are in T form ( )
polymers are a mixture of T form ( ) and D form ( )
minus-end addition is slow—
hydrolysis catches up
(A)
POLYMERIZATION FOLLOWED
BY NUCLEOTIDE HYDROLYSIS
– +
– +
C c (T) < C c (D)
plus-end addition is fast—
hydrolysis lags behind
while the total length of the filament remains unchanged. This “steady-state treadmilling”
requires a constant consumption of energy in the form of ATP hydrolysis.
The Functions of Actin Filaments Are Inhibited by Both Polymerstabilizing
and Polymer-destabilizing Chemicals
Chemical compounds that stabilize or destabilize actin filaments are important
tools in studies of the filaments’ dynamic behavior and function in cells. The cytochalasins
are fungal products that prevent actin polymerization by binding to the
MBoC6 m16.14/16.14
plus end of actin filaments. Latrunculin prevents actin polymerization by binding
to actin subunits. The phalloidins are toxins isolated from the Amanita mushroom
that bind tightly all along the side of actin filaments and stabilize them against
depolymerization. All of these compounds cause dramatic changes in the actin
cytoskeleton and are toxic to cells, indicating that the function of actin filaments
depends on a dynamic equilibrium between filaments and actin monomers
(Table 16–1).
grow
elongation rate
(B)
0
shrink
C c (T)
treadmilling range
C c (D)
subunit
concentration
For C c (T) < C < C c (D)
treadmilling occurs
at T
plus
end
at D
minus
end
Figure 16–14 Treadmilling of an actin
filament, made possible by the ATP
hydrolysis that follows subunit addition.
(A) Explanation for the different critical
concentrations (C c ) at the plus and minus
ends. Subunits with bound ATP (T-form
subunits) polymerize at both ends of
a growing filament, and then undergo
nucleotide hydrolysis within the filament. As
the filament grows, elongation is faster than
hydrolysis at the plus end in this example,
and the terminal subunits at this end are
therefore always in the T form. However,
hydrolysis is faster than elongation at the
minus end, and so terminal subunits at
this end are in the D form. (B) Treadmilling
occurs at intermediate concentrations of
free subunits. The critical concentration for
polymerization on a filament end in the
T form is lower than for a filament end
in the D form. If the actual subunit
concentration is somewhere between these
two values, the plus end grows while the
minus end shrinks, resulting in treadmilling.
Actin-Binding Proteins Influence Filament Dynamics and
Organization
In a test tube, polymerization of actin is controlled simply by its concentration, as
described above, and by pH and the concentrations of salts and ATP. Within a cell,
however, actin behavior is also regulated by numerous accessory proteins that
bind actin monomers or filaments (summarized in Panel 16–3). At steady state
Table 16–1 Chemical Inhibitors of Actin and Microtubules
Chemical
Effect on
filaments
Mechanism
Original source
Actin
Latrunculin Depolymerizes Binds actin subunits Sponges
Cytochalasin B Depolymerizes Caps filament plus ends Fungi
Phalloidin Stabilizes Binds along filaments Amanita mushroom
Microtubules
Taxol ®
(paclitaxel)
Stabilizes Binds along filaments Yew tree
Nocodazole Depolymerizes Binds tubulin subunits Synthetic
Colchicine Depolymerizes Caps filament ends Autumn crocus