Autophosphorylated CaMKIIalpha acts as a scaffold to recruit proteasomes to dendritic spines.
The molecular mechanisms regulating the ubiquitin proteasome system (UPS) at synapses are poorly understood. We report that CaMKIIalpha-an abundant postsynaptic protein kinase-mediates the activity-dependent recruitment of proteasomes to dendritic spines in hippocampal neurons. CaMKIIalpha is biochemically associated with proteasomes in the brain. CaMKIIalpha translocation to synapses is required for activity-induced proteasome accumulation in spines, and is sufficient to redistribute proteasomes to postsynaptic sites. CaMKIIalpha autophosphorylation enhances its binding to proteasomes and promotes proteasome recruitment to spines. In addition to this structural role, CaMKIIalpha stimulates proteasome activity by phosphorylating proteasome subunit Rpt6 on Serine 120. However, CaMKIIalpha 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 CaMKIIalpha in activity-dependent proteasome redistribution, which is commensurate with the great abundance of CaMKIIalpha in synapses.
Bingol
Baris
B
The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences and Biology, Massachusetts Institute of Technology, Cambridge, 02139, USA.
Wang
Chi-Fong
CF
Arnott
David
D
Cheng
Dongmei
D
Peng
Junmin
J
Sheng
Morgan
M
D000818:Animals; D001921:Brain / Q000166:cytology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D009474:Neurons / Q000166:cytology; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D013569:Synapses
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D046988:Proteasome Endopeptidase Complex