Table I.
Actin-binding proteins and signaling pathways in dendritic spine morphogenesis
| Protein | Effect on actin cytoskeletona | Function in dendritic spine morphogenesis | Signaling pathwaya |
| Nucleating | |||
| Arp2/3 complex | Nucleates branched actin filaments | Required for spine head growth (Wegner et al., 2008; Hotulainen et al., 2009) | Rac and Cdc42 signaling cascades activate Arp2/3 complex |
| DRF3/ mDia2 | Induces elongation of straight actin filaments | Required for proper dendritic filopodia and spine neck formation (Hotulainen et al., 2009) | Rif activates DRF3/mDia2 |
| Proteins regulating Arp2/3 complex | |||
| Cortactin | Activates Arp2/3 complex | Regulates spine density; binds Shank (Hering and Sheng, 2003) | Src family kinases activate cortactin |
| N-WASP | Activates Arp2/3 complex | Regulates spine density (Wegner et al., 2008) | Cdc42, Rac, and PIP2 activate N-WASP |
| WAVE-1 | Activates Arp2/3 complex | Regulates spine density (Soderling et al., 2007) | Rac and PIP3 binding activate WAVE-1 |
| Abp1 | Controls Arp2/3 via N-WASP | Abp1 expression increases mushroom spine; binds Shank (Haeckel et al., 2008) | |
| ADP/ATP exchanger | |||
| Profilin | Enhances exchange of ADP to ATP and actin treadmilling rate | Stabilizes spine morphology and moves to spines upon activity (Ackermann and Matus, 2003) | |
| Depolymerizing | |||
| ADF, Cofilin | Depolymerizes and severs actin filaments | Required for spine head morphology and stabilization during LTP formation (Chen et al., 2007; Hotulainen et al., 2009) | PAK3 phosphorylates LIM kinase, which inactivates ADF/cofilins |
| Capping | |||
| Eps8 | Caps plus-ends of actin filaments | Inhibits BDNF-induced neuronal filopodia formation (Menna et al., 2009) | MAPK phosphorylation inhibits Eps8 |
| Cross-linking | |||
| α-Actinin | Bundles actin filaments | Expression induces spine elongation and thinning (Hoe et al., 2009) | FAK reduces binding of α-actinin to actin |
| Calponin | Bundles and stabilizes actin filaments | Expression induces spine elongation and increase in density (Rami et al., 2006) | |
| CaMKIIβ | Bundles and stabilizes actin filaments | Required for spine maturation and LTP-induced stabilization (Okamoto et al., 2007) | CaMKIIβ autoinhibition is released by NMDA receptor activation |
| Neurabin I | Bundles actin filaments | Required for spine maturation (Terry-Lorenzo et al., 2005) | Cdk5 phosphorylation inhibits Neurabin I |
| Drebrin | Bundles and stabilizes actin filaments | Expression induces spine elongation (Ivanov et al., 2009) | |
| Motor proteins | |||
| Myosin II | ATP-driven, actin-based motor | Required for proper spine head and neck morphology (Ryu et al., 2006) | RhoA activates myosin II |
| Myosin VI | ATP-driven, actin-based motor | Required for spine formation (Osterweil et al., 2005) |
a
For review see Le Clainche and Carlier, 2008.