Membrane targeting of WAVE2 is not sufficient for WAVE2-dependent actin polymerization: a role for IRSp53 in mediating the interaction between Rac and WAVE2

Eps8 Protein Facilitates Phagocytosis by Increasing TLR4-MyD88 Protein Interaction in Lipopolysaccharide-stimulated Macrophages

“…As compared with their family members, WASP and WAVE2 are predominantly expressed in macrophages (46,47). Whereas WASP is required for ␤1 integrin-mediated actin reorganization during phagocytosis of pathogens (48), WAVE2 is indispensable for mobilization that needs the participation of Abi1 and IRSp53 in CSF-1-stimulated macrophages (47,49). Interestingly, to date, no paper concerning the role of WAVE2 in macrophage phagocytosis has been published.…”

CSF-1 Receptor Signaling in Myeloid Cells

“…Rac2 initially increases, but subsequently inhibits PLD2 activity, by preventing PLD interaction with PIP2 at the plasma membrane, thus leading to cell immobilization (Peng et al 2011). Although the above studies in macrophage cell lines indicate that Rac1 and Rac2 are required for chemotaxis Abou-Kheir et al 2008), the findings are in conflict with those in primary macrophages, in which absence of Rac1, Rac2, or both, did not affect CSF-1-induced chemotaxis (Wells et al 2004;Wheeler et al 2006). An additional conflict relates to the mechanism of Rac1 activation by CSF-1R.…”

“…The second wave of actin polymerization leading to membrane ruffling involves Rac1/ IRSp53 activation of the WAVE2/Abi complex (Kheir et al 2005;Abou-Kheir et al 2008) and is pTyr-721/PI3K independent (Sampaio et al 2011). CSF-1R-regulated membrane ruffling also requires PLD2 lipase and Rac2 GEF activities (Mahankali et al 2011a,b).…”

mDia1 and WAVE2 Proteins Interact Directly with IRSp53 in Filopodia and Are Involved in Filopodium Formation

“…The WAVE homology domain allows WAVE proteins to function as a multiprotein WAVE complex by binding directly to Abelson-interacting protein and hematopoietic stem/progenitor cell protein C300 (HSPC300), indirectly to Nck-associated protein 1 (NAP1), and specifically to Rac1-associated protein 1 (SRA1), while the VCA region brings together the Arp2/3 complex and an actin monomer to facilitate actin polymerization (26). Interaction of IRSp53 with the proline-rich region of WAVE2 is believed to mediate WAVE2 activity downstream of Rac (27). WAVE1 has been linked to the formation of dorsal ruffles, while WAVE2 has been implicated in both peripheral ruffle (28) and filopodial protrusion (29,30) and demonstrated to be essential for lamellipodia (31,32).…”