Biology Reference
In-Depth Information
authors) of WASp has been used to study the binding of WASp to actin; this
domain binds to a single actin monomer with a K
d
of 0.6 mM, and to the Arp2/
3 complex with a K
d
of 0.6 mM (Marchand et al., 2001). Although WASp and
Scar proteins bind to the Arp2/3 complex and to actin with nearly identical
anities, they do not activate it to the same extent. Scar induces a
substantially slower rate of nucleation, while WASp and N-WASp activities
are 16 and 70-fold higher, respectively, relative to Scar 1. This difference
appears to be due to differing numbers of acidic amino acids at the C-terminus
(Zalevsky et al., 2001b).
A number of extra factors have been implicated in the correct functioning of
WASp family proteins. It is clear that the control of the actin cytoskeleton is
more complex than is often described, for example by assigning single
GTPases to specific structures. Cdc42 is frequently described as leading to
filopodia production via N-WASp, with Rac simply leading to lamellipodia
via Scar. In Dictyostelium, multiple filopodia are formed in the absence of
Cdc42, while different activated Rac proteins induce actin structures of
different shape and stability, in different parts of the cell.
How does the actin-polymerization machinery of the cell produce distinct
actin structures?
All motile cells, from single-celled organisms such as Dictyostelium to motile
cells from the human body, use their actin polymerization to produce a variety
of different actin structures with different uses. Although the identities of most
of the major players in actin filament production are now known, the ways
that the relatively small number of proteins interact to produce different
structures is a much more complex problem. At present it is unknown if
organization of actin is determined by the mechanism of actin polymerization
itself, or if the actin filaments are organized by actin binding proteins after
polymerization.
The Arp2/3 complex is found at the sides of pre-existing actin filaments, and
activators like the WASp family cause it to generate a branched network
(Blanchoin et al., 2000; Mullins et al., 1998). However, the precise pathways
that lead to the generation of various different actin structures such as
filopodia, lamellipodia and membrane ru
es are unknown. Perhaps the
scaffolding properties of the WASp family adaptor proteins are important,
allowing interaction with a number of proteins resulting in greater sensitivity
to different signals and leading to a larger number of outcomes. Also, other
components of the large complexes which include the WASp family, such as
profilins, may be involved in modulating or bringing together cytoskeletal
elements and signalling molecules such as Rho GTPases, in specific areas of
the cell (Witke et al., 1998).
