Biology Reference
In-Depth Information
Introduction
A brief summary of the process of actin dynamics
In the cytosol, ATP-G-actin is kept in a readily polymerizable pool bound to
profilin. Profilin-actin is thought to be recruited to the site of polymerization
via the poly-Pro motifs of activator proteins like VASP or WASp. Because de
novo nucleation of filaments is rate-limiting, the Arp2/3 complex, the major
cellular F-actin nucleator, lays at the core of cytoskeleton dynamics. Recent
advances propose that extracellular signals are relayed through effector
proteins like Rho family GTPases to the WASp or Scar family proteins, which
in turn lead to the localized recruitment and activation of the Arp2/3 complex
(Pollard et al., 2000). Nucleation occurs mainly by branching off existing
filaments, and polymerization of ATP-G-actin is thought directly to produce
the force necessary to push membranes. Rapidly, capping of the newly
generated filament is followed by stabilization through a variety of actin
binding proteins. Binding of ADF/cofilin to ADP-F-actin initiates depoly-
merization. The pool of ATP-G-actin is reconstituted by the nucleotide
exchange factor profilin (Blanchoin et al., 2000). It has been recently
demonstrated that this Arp2/3-dependent mechanism, possibly being the
major one, nevertheless does not account for all engagements of the actin
polymerization machinery. For example, PAK kinase can recruit and
phosphorylate filamin proteins and together generate orthogonally cross-
linked actin meshworks (Vadlamudi et al., 2002). As another alternative, to
generate unbranched actin filaments, proteins of the formin family work
downstream of Rho GTPases and appear able to nucleate filaments and stay
associated with their growing barbed ends (Pruyne et al., 2002). The dendritic
nucleation model offers a solid framework to dissect further the mechanisms
of actin dynamics and their involvement in a vast array of cellular processes,
and some questions are beginning to find an answer (Figure 3.1).
The myosin superfamily
The myosin superfamily of mechanoenzymes comprises 18 classes (Berg et al.,
2001). For example, the human genome encodes about 40 myosin genes of
which about 25 are unconventional and come from at least 11 classes;
D. discoideum appears to have 13 myosins from about six classes (Glockner et
al., 2002) and Saccharomyces cerevisiae has five myosins from three classes
(Berg et al., 2001). All members of the myosin family share a common
structure; they are composed of three modules, the head, neck and tail
domains. The N-terminal region harbours the motor unit, utilizing ATP
to power movement along actin filaments. Almost all myosins follow the
