Figure 1.

Influence of c-Abl on dendritic spines.

Upper panel: Dendritic spines are synaptic compartments with an electron dense zone, the post-synaptic density (PSD), mostly containing PSD-95 and Shank. N-methyl-D-aspartate receptors (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoazolepropionate receptors (AMPAR) are attached to the PSD through PDZ domains. Ephrin A4 receptors respond to Aβ-oligomers (AβOs) binding, activating c-Abl to promote neurodegeneration. EphA4, PSD-95 (Y533), F-actin associated proteins Rho/Rac, Rho-associated protein kinase (ROCK), WASP-family verprolin-homologous protein (WAVE) (Y150) and Abi are regulated by c-Abl. Shape changes during maturation are illustrated by confocal microscopy sections of dendritic spines: filopodia (most immature), thin, stubby, mushroom (most mature), branched, or two-headed spines. Bottom panels: c-Abl alters spine density and induces a shift in the morphology of dendritic spines. c-Abl knock-out (c-Abl-KO) mice subjected to cognitive training (MWM: Morris water maze) show increased spine density and display hippocampal neurons that are enriched in mature forms such as mushroom spines (left). AβOs-induced synaptotoxicity decreases spine density independent of c-Abl, and promotes enlargement of spines increasing filopodia, especially in c-Abl-KO neurons. AβOs normally induce apoptosis, but the absence of c-Abl prevents it (right).