Biology Reference
In-Depth Information
pathway of disassembly. One factor is the ability of ADF/cofilin to sever
filaments, creating ends for subunit dissociation. ADF/cofilin may also
promote subunit dissociation from these ends. Further work is required to
firm up both the mechanism and the kinetics of disassembly.
Some cellular actin filaments, including those in stress fibres and filopodia
turn over slowly. Binding of tropomyosin may contribute to their stability,
since it protects filaments from severing by ADF/cofilin (Maciver et al., 1991)
and also inhibits branching by the Arp2/3 complex (Blanchoin et al.,
2000b).
Recycling ADP-actin subunits
ADF/cofilin binds ADP-actin tighter than ATP-actin and also inhibits
exchange of the bound ADP, so it might trap ADP-actin when it dissociates
from filaments. However, both profilin and ADF/cofilin are in rapid equilibria
with ADP-actin (Perelroizen et al., 1994; Vinson et al., 1998; Blanchoin and
Pollard, 1998). Bound profilin promotes rapid dissociation of ADP and the
high cytoplasmic concentration of ATP relative to ADP results in nucleotide-
free actin binding ATP (Vinson et al., 1998). ATP-actin binds profilin much
better than ADF/cofilin, refilling the pool of ATP-actin (Rosenblatt et al.,
1995) ready for elongation of barbed ends.
Reaction to a chemoattractant
Chemoattractants activate parallel signalling pathways employing Rho-family
GTPases, which promote actin polymerization locally by at least two
mechanisms: creation of new barbed ends as branches by activating Arp2/3
complex; and inhibition of ADF/cofilin, which tends to stabilize existing
filaments. Alternatively, or in addition, some activators may transiently
activate ADF/cofilin by dephosphorylation, promoting severing and the
growth of barbed ends which are favourable for branching nucleation by the
Arp2/3 complex (Zebda et al., 2000; Ichetovkin et al., 2002).
Reaction to the withdrawal of a chemoattractant
The whole system runs down automatically in the absence of a positive signal
for assembly. Lacking activators, nucleation-promoting factors will return to
their inhibited states. The rate of decay will be determined by the rate of GTP
hydrolysis by the Rho-family GTPases. It is not known if any of the
nucleation-promoting factors are GTPase activators (GAPs), like effectors of
