Targeted protein degradation and synapse remodeling by an inducible protein kinase |
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| Authors: | Pak Daniel T S Sheng Morgan |
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| Institution: | Picower Center for Learning and Memory, RIKEN Massachusetts Institute of Technology (MIT) Neuroscience Research Center, Howard Hughes Medical Institute, MIT, Cambridge, MA 02139, USA. dtp6@georgetown.edu |
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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. |
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