The actin-binding protein Abp1 controls dendritic spine morphology and is important for spine head and synapse formation.

Polymerization and organization of actin into complex superstructures, including those found in dendritic spines, is indispensable for structure and function of neuronal networks. Here we show that the filamentous actin (F-actin)-binding protein 1 (Abp1), which controls Arp2/3 complex-mediated actin nucleation and binds to postsynaptic scaffold proteins of the ProSAP (proline-rich synapse-associated protein 1)/Shank family, has a profound impact on synaptic organization. Overexpression of the two Abp1 F-actin-binding domains increases the length of thin, filopodia-like and mushroom-type spines but dramatically reduces mushroom spine density, attributable to lack of the Abp1 Src homology 3 (SH3) domain. In contrast, overexpression of full-length Abp1 increases mushroom spine and synapse density. The SH3 domain alone has a dominant-negative effect on mushroom spines, whereas the density of filopodia and thin, immature spines remains unchanged. This suggests that both actin-binding and SH3 domain interactions are crucial for the role of Abp1 in spine maturation. Indeed, Abp1 knockdown significantly reduces mushroom spine and synapse density. Abp1 hereby works in close conjunction with ProSAP1/Shank2 and ProSAP2/Shank3, because Abp1 effects were suppressed by ProSAP2 RNA interference and the ProSAP/Shank-induced increase of spine head width is further promoted by Abp1 cooverexpression and reduced on Abp1 knockdown. Also, interfering with the formation of functional Abp1-ProSAP protein complexes prevents ProSAP-mediated spine head extension. Spine head extension furthermore depends on local Arp2/3 complex-mediated actin polymerization, which is controlled by Abp1 via the Arp2/3 complex activator N-WASP (neural Wiskott-Aldrich syndrome protein). Abp1 thus plays an important role in the formation and morphology control of synapses by making a required functional connection between postsynaptic density components and postsynaptic actin dynamics.