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Published Online October 23, 2003
Science DOI: 10.1126/science.1082475

Research Articles

Submitted on January 17, 2003
Accepted on September 22, 2003

Targeted Protein Degradation and Synapse Remodeling by an Inducible Protein Kinase

Daniel T. S. Pak 1* Morgan Sheng 2*

1 Picower Center for Learning and Memory, RIKEN-MIT Neuroscience Research Center, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Present address: Georgetown University, Department of Pharmacology, Washington, DC 20057, USA.
2 Picower Center for Learning and Memory, RIKEN-MIT Neuroscience Research Center, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

* To whom correspondence should be addressed. E-mail: dtp6{at}georgetown.edu, msheng{at}mit.edu.

Synaptic plasticity involves the reorganization of synapses, at the protein and 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 SPAR, a postsynaptic RapGAP and actin regulatory protein, leading to degradation of SPAR. Induction of SNK in hippocampal neurons eliminated SPAR protein, depleted PSD-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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