Targeted protein degradation and synapse remodeling by an inducible protein kinase.
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. dtp6@georgetown.edu
Daniel T S
DT
Pak
Morgan
M
Sheng
D000199:Actins / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003712:Dendrites / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D004790:Enzyme Induction; D005455:Fluorescent Antibody Technique; D020690:GTPase-Activating Proteins / Q000032:analysis / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D007150:Immunohistochemistry; D009097:Multienzyme Complexes / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011554:Pseudopodia / Q000648:ultrastructure; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D014162:Transfection; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D000199:Actins; D020690:GTPase-Activating Proteins; D009097:Multienzyme Complexes; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C479629:Sipa1l1 protein, rat; D025801:Ubiquitin; C033652:postsynaptic density proteins; D044767:Ubiquitin-Protein Ligases; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C444640:serum-inducible kinase; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex