Actin Filament Assembly: The Search for a Barbed End - Cell Motility: From Molecules to Organisms - page 135

Figure 8.1 The WASp family proteins and their interactions. SHD ¼ Scar homology
domain, PRO ¼ proline-rich region, WH2 ¼ WASp homology 2 actin monomer-binding
domain, C ¼ central basic domain, A ¼ Arp2/3 complex-binding domain, WH1 ¼ WASp
homology 1, GBD ¼ GTPase binding domain
All members of the WASp family show considerable conservation,
particularly in their C-terminal domain containing three common motifs
(Figure 8.1). A central proline rich region (PRO) that can bind to SH3
domain-containing proteins such as the adapter protein Nck and thus
indirectly associate with receptor tyrosine kinases (Rivero-Lezcano et al.,
1995); a WH2 (WASp homology 2) domain that binds monomeric actin, a
central basic patch of amino acids that appears to be important both for actin
and Arp2/3 complex binding (C) and at the extreme C-terminus a region of
net negative charge A (Acidic) that binds to the Arp2/3 complex (Machesky
and Insall, 1998). Both WASp and N-WASp also contain a GTPase binding
domain (GBD) that binds to Cdc42 (Aspenstrom et al., 1996). The N-terminal
regions of WASp and N-WASp also interact with PIP 2 in vitro (Miki et al.,
1996) (see also Chapter 9).
The WASp-Arp2/3 pathway
WASp and Scar1 bind to the Arp2/3 complex via the p21-Arc subunit and
likely other subunits as well. Over-expression of C-terminal fragments of
Scar1 and WASp results in both delocalization of the Arp2/3 complex and loss
of lamellipodia and actin spots (Machesky and Insall, 1998). Cdc42 and PIP 2
as well as adapter proteins (Nck and Grb2) also activate WASp and N-WASp.
Thus the discovery of these connections provided an insight for a complete
signalling pathway from external stimuli to controlled actin polymerization:
the WASp-Arp2/3 pathway (Figure 8.2).