Biology Reference
In-Depth Information
intracellular pathogen L. monocytogenes (Welch et al., 1997b). In these
experiments Arp2/3 complex isolated from human platelets is su
cient for the
induction of actin polymerization and motility at the cell surface of the
bacterium. Since then the Arp2/3 complex has been shown to both nucleate
the formation of new actin filaments, crosslink existing filaments and cap the
pointed end with high anity, leading to the proposition of the now widely
accepted dendritic nucleation model of actin organization in lamellipodium
protrusion (Mullins et al., 1998) (see also Chapter 1).
The many roles of the Arp2/3 complex in vivo are rapidly being uncovered.
For example the Arp2/3 complex has been shown to be necessary for
phagocytosis in mammals and the amoeba Dictyostelium discoideum (Insall
et al., 2001; May et al., 2000), endocytosis in yeast (Warren et al., 2002) and
macropinocytosis (Insall et al., 2001). The Arp2/3 complex also appears to be
involved in cell polarity establishment and migration in fibroblast monolayers
in a wound-healing model (Magdalena et al., 2003). Studies utilizing loss of
function mutations in the Drosophila homologues of p41-Arc and Arp3 also
reveal a requirement for the Arp2/3 complex for ring-canal expansion during
oogenesis but not for the formation of parallel actin bundles in the cytoplasm
of nurse cells (Hudson and Cooley, 2002). In Drosophila, the Arp2/3 complex
is also required for embryogenesis, as pseudocleavage furrow assembly,
necessary for proper embryonic cell division, is disrupted when a mutation in
the p41-Arc subunit is introduced (Stevenson et al., 2002). Arp2/3 complex-
dependent actin polymerization is also necessary for actin polymerization in
platelets, leading to the formation of filopodia and lamellipodia (Li et al.,
2002).
Purified Arp2/3 complex nucleates actin filaments with free barbed ends,
but this activity is very weak (Mullins et al., 1998). However, several proteins
activate the complex at sites of new actin polymerization. Of these, the most
well-understood are members of the WASp family, which sport domains that
interact with signalling molecules (such as the small GTPases Rac and Cdc42,
G-proteins and tyrosine kinases), actin monomers and the Arp2/3 complex
(Machesky and Insall, 1998).
WASp family proteins
The WASp family consists of five proteins in mammals: WASp, N-WASp and
Scar1-3 (also known as WAVE1-3). WASp is expressed only in haemato-
poietic cells and when mutated results in Wiskott-Aldrich syndrome (WAS), a
rare X-linked disease, in which sufferers have severely impaired immune
function (Derry et al., 1994). N-WASp is more widely expressed, as are the
Scars. Scar was originally identified in Dictyostelium in a screen for
s
uppressors of a
cA
MP
r
eceptor mutation (Bear et al., 1998).
