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.
Pak
Daniel T S
DT
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
Sheng
Morgan
M
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