Autophosphorylated CaMKIIα Acts as a Scaffold to Recruit Proteasomes to Dendritic Spines

SummaryThe molecular mechanisms regulating the ubiquitin proteasome system (UPS) at synapses are poorly understood. We report that CaMKIIα—an abundant postsynaptic protein kinase—mediates the activity-dependent recruitment of proteasomes to dendritic spines in hippocampal neurons. CaMKIIα is biochemically associated with proteasomes in the brain. CaMKIIα translocation to synapses is required for activity-induced proteasome accumulation in spines, and is sufficient to redistribute proteasomes to postsynaptic sites. CaMKIIα autophosphorylation enhances its binding to proteasomes and promotes proteasome recruitment to spines. In addition to this structural role, CaMKIIα stimulates proteasome activity by phosphorylating proteasome subunit Rpt6 on Serine 120. However, CaMKIIα translocation, but not its kinase activity, is required for activity-dependent degradation of polyubiquitinated proteins in spines. Our findings reveal a scaffolding role of postsynaptic CaMKIIα in activity-dependent proteasome redistribution, which is commensurate with the great abundance of CaMKIIα in synapses.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (287 K)Download as PowerPoint slideHighlights► The protein kinase CaMKIIα associates with proteasomes in the brain ► CaMKIIα translocation to synapses is required for proteasome redistribution ► Autophosphorylated CaMKIIα acts as a scaffold to promote proteasome recruitment ► CaMKIIα is required for activity-induced protein turnover in spines