Linkage of the Actin Cytoskeleton to the Postsynaptic Density via Direct Interactions of Abp1 with the ProSAP/Shank Family

摘要: Synaptic contacts contain elaborate cytomatrices on both sides of the synaptic cleft, which are believed to organize and link different functions in time space can respond inner outer cues with massive structural reorganizations. At PSD (postsynaptic density), activity-dependent reorganizations cortical actin cytoskeleton hypothesized play a role plasticity. Here, we report interactions F-actin binding protein Abp1 members ProSAP/Shank family: multidomain scaffolding proteins interconnecting glutamate receptors other components. Affinity-purification experiments demonstrate that mediated by (actin-binding 1) SH3 (Src homology 3) domain, associates proline-rich motif is conserved within C-terminal parts ProSAP1(proline-rich synapse-associated 1)/Shank2 ProSAP2/Shank3. The distribution Abp1, ProSAP1, ProSAP2 overlaps brain, all three part particularly enriched cortex hippocampus. Coimmunoprecipitation endogenous colocalization studies ProSAPs hippocampal neurons indicate vivo relevance interactions. Intriguingly, recruitment assays bind dynamic structures simultaneously, suggesting might organizing elements PSD. Importantly, paradigms neuronal stimulation induce redistribution ProSAP-containing synapses. Our data suggest may serve localize dendritic spines, thus serving as attachment points for postsynaptic cytoskeleton. This creates functional connection between cytoskeletal rearrangements.