Targeted Protein Degradation and Synapse Remodeling by an Inducible Protein Kinase

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Abstract
Synaptic plasticity involves the reorganization of synapses at the protein and the morphological levels. Here, we report activity-dependent remodeling of synapses by serum-inducible kinase (SNK). SNK was induced in hippocampal neurons by synaptic activity and was targeted to dendritic spines. SNK bound to and phosphorylated spine-associated Rap guanosine triphosphatase activating protein (SPAR), a postsynaptic actin regulatory protein, leading to degradation of SPAR. Induction of SNK in hippocampal neurons eliminated SPAR protein, depleted postsynaptic density–95 and Bassoon clusters, and caused loss of mature dendritic spines. These results implicate SNK as a mediator of activity-dependent change in the molecular composition and morphology of synapses.