Biology Reference
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Figure 9.3 Mechanism activation of WAVE1. Under resting conditions, WAVE1 is
inactive in a complex with Nap125, PIR121, Abi2, and HSPC300. When cells are
stimulated, active Rac binds Nap-PIR-Abi2, and causes them to dissociate from WAVE1-
HSPC, resulting in the activation of WAVE1
Nap125 (NCK-associated protein), Abi2 and HSPC300. In this complex,
activity of WAVE1 is suppressed. However, active Rac or Nck caused
dissociation of WAVE1 and HSCP300 from the complex. This dissociation
releases WAVE1, which is thought to be constitutively active by itself,
resulting in actin nucleation through Arp2/3 complex activation. However, it
remains unclear whether this activation mechanism is valid for other WAVEs
or if WAVE1 and WAVE2 are regulated differently.
N-WASp is involved in podosome formation and tubulogenesis
Podosomes occur specifically in monocyte-derived haematopoietic cells
including macrophages and osteoclasts. Podosomes contain cell adhesion
integrin receptors and several actin-regulating proteins such as cortactin, talin
and vinculin that link integrins to the actin cytoskeleton. Podosome formation
is also observed in cells transformed with the v-src oncogene. Podosome
formation allows transformed cells to invade into extracellular matrix. N-
WASp was found to localize at podosomes but WAVEs are not present in this
area. Expression of a dominant-negative N-WASp, DV N-WASp, disrupted
formation of podosomes, suggesting that N-WASp is crucial for podosome
formation (Mizutani et al., 2002). However, it is unclear how N-WASp
localizes at podosomes. Because cortactin and N-WASp co-localize at
podosomes, it is possible that cortactin recruits N-WASp through its SH3
domain. Indeed, the SH3 domain of cortactin binds to N-WASp. In addition,
