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Science. 2003 Nov 21;302(5649):1368-73. Epub 2003 Oct 23.

Targeted protein degradation and synapse remodeling by an inducible protein kinase.

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  • 1Picower 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

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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PMID:
14576440
DOI:
10.1126/science.1082475
[PubMed - indexed for MEDLINE]
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