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Science 302 (5649): 1368-1373

Copyright © 2003 by the American Association for the Advancement of Science

Targeted Protein Degradation and Synapse Remodeling by an Inducible Protein Kinase

Daniel T. S. Pak*{dagger}, and Morgan Sheng{dagger}

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.

Picower Center for Learning and Memory, RIKEN Massachusetts Institute of Technology (MIT) Neuroscience Research Center, Howard Hughes Medical Institute, MIT, Cambridge, MA 02139, USA.

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* Present address: Department of Pharmacology, Georgetown University, Washington, DC 20057, USA.

{dagger} To whom correspondence should be addressed. Email: dtp6{at}georgetown.edu (D.T.S.P.); msheng{at}mit.edu (M.S.)

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