Overlapping expression pattern of the actin organizers Spir-1 and formin-2 in the developing mouse nervous system and the adult brain

Structural and functional insights into the Spir/formin actin nucleator complex

“…A functional cooperation of Spir and FMN formins was further supported by gene expression analysis of the spir-1 and formin-2 genes during mouse embryogenesis and in adult mouse tissues (Schumacher et al, 2004). The genes of the cooperating actin nucleators have a very restricted but highly overlapping expression pattern.…”

“…The genes of the cooperating actin nucleators have a very restricted but highly overlapping expression pattern. Next to oocytes and testis, the spir-1 and formin-2 genes are highly expressed in developing nervous system and neuronal cells of the adult nervous system (Schumacher et al, 2004;Pfender et al, 2011). Despite the predominant expression throughout the nervous system, mouse genetic analysis of formin-2 and Spir-1 function did not reveal any gross neural abnormalities (Leader et al, 2002;Peleg et al, 2010;Sandra Pleiser, Mumna Al Banchaabouchi, and Eugen Kerkhoff, unpublished data) (Table 1).…”

Formins at a glance

“…In vivo, Bni1-Bud6 and APC-mDia1 function together to assemble actin cables and pseudocleavage furrows, respectively, and have also been shown to directly interact in vitro to assemble actin in the presence of profilin and/or capping protein Okada et al, 2010;Graziano et al, 2011;Breitsprecher et al, 2012). Spire and FMN co-function in vivo to assemble cytoplasmic actin meshworks (Schumacher et al, 2004;Pfender et al, 2011;Schuh, 2011) but, perplexingly, Spire inhibits rather than enhances the nucleation activity of FMN in vitro (Quinlan et al, 2007;Vizcarra et al, 2011;Zeth et al, 2011), suggesting that additional factors are required to activate collaborative actin assembly through Spire-FMN. More recently, we have begun to address the question of how NPF-formin pairs co-assemble actin filaments by using triple-color total internal reflection fluorescence (TIRF) microscopy at the single-molecule level .…”

Kinetic-structural analysis of neuronal growth cone veil motility

“…However, other studies interfering with Arp function (Di Nardo et al, 2005;Gupton et al, 2005;Ng and Luo, 2004;Strasser et al, 2004) have reported continued motility, thus suggesting the existence of Arp2/3-independent mechanisms of protrusion. Finally, recent literature has identified actin nucleators other than Arp2/3 -namely, formins (Evangelista et al, 2003;Kovar, 2006;Zigmond, 2004) and spire proteins (Baum and Kunda, 2005;Quinlan et al, 2005;Schumacher et al, 2004), both of which nucleate linear actin filaments as opposed to branched ones. Such non-Arp nucleators taken together with the Arp depletion and perturbation experiments suggest that redundant pathways may exist for the protrusion of lamellipodia and veils.…”