Biology Reference
In-Depth Information
actin polymerization. The adapter protein Nck can also induce this
dissociation suggesting an additional pathway for Scar activation (Eden et
al., 2002). The relative contributions of Nck and Rac1 in modifying Scar
activity are however unknown.
Thus, while it is apparent that signals from many cellular receptors
converge on the common WASp-Arp2/3 pathway, the many roles of WASp
proteins in the cell are only beginning to be understood. N-WASp has been
localized to actin comets that propel intracellular vesicles (Rozelle et al.,
2000) and in N-WASp-defective cells, actin comets are not observed
(Benesch et al., 2002). The adapter proteins Nck, Grb2 and WIP have
also been implicated in the recruitment of N-WASp to the vesicle surface
(Benesch et al., 2002) and the large GTPase dynamin, important in
triggering the pinching off nascent vesicles from both the Golgi apparatus
and plasma membrane, is co-localized to actin in comet structures (Orth et
al., 2002). N-WASp has also been identified as a downstream effector of
Cdc42 important in regulating the retrograde transport of proteins from the
Golgi apparatus to the endoplasmic reticulum (Luna et al., 2002). The
physiological significance of actin in such vesicle tra
cking is not under-
stood but these results provide mounting evidence that there is a direct link
between actin and membrane dynamics.
Cdc42-activated N-WASp is also implicated in filopodium formation (Miki
et al., 1998a) although more recent studies using N-WASp-defective cell lines
have shown that Cdc42-mediated filopodium formation is unaffected and thus
may provide evidence of an alternative mechanism leading to their formation
(Snapper et al., 2001).
It is well documented that WASp is required for proper development of
leukocytes and the immune system (Thrasher et al., 2000). Recently, however,
studies in Drosophila have revealed an interesting requirement of the WASp
homologue Wsp in the control of cell fate decisions mediated by Notch. Ben-
Yaacov and colleagues show that flies with mutant Wsp are unable to undergo
normal sensory organ development resulting in increased neuronal differ-
entiation at the expense of other cell types (Ben-Yaacov et al., 2001). As
Notch signalling is believed to involve receptor-mediated endocytosis the
authors postulate that WASp may function to link endocytosis of Notch with
the underlying actin cytoskeleton.
Compared with WASp/N-WASp, the cellular roles of the Scar proteins
have been more elusive. In the first studies of their kind, Zallen and co-
workers have examined the role of the Drosophila homologue of Scar and
the Arp2/3 complex during embryonic development and found both are
required for proper cell shape and motility (Zallen et al., 2002). Interestingly,
WASp was not required for these events providing evidence that the Arp2/3
complex governs distinct cellular events dependent on either Scar or WASp
activation.
