Regulation of postsynaptic RapGAP SPAR by Polo-like kinase 2 and the SCFbeta-TRCP ubiquitin ligase in hippocampal neurons.
The ubiquitin-proteasome pathway (UPP) regulates synaptic function, but little is known about specific UPP targets and mechanisms in mammalian synapses. We report here that the SCF(beta-TRCP) complex, a multisubunit E3 ubiquitin ligase, targets the postsynaptic spine-associated Rap GTPase activating protein (SPAR) for degradation in neurons. SPAR degradation by SCF(beta-TRCP) depended on the activity-inducible protein kinase Polo-like kinase 2 (Plk2). In the presence of Plk2, SPAR physically associated with the SCF(beta-TRCP) complex through a canonical phosphodegron. In hippocampal neurons, disruption of the SCF(beta-TRCP) complex by overexpression of dominant interfering beta-TRCP or Cul1 constructs prevented Plk2-dependent degradation of SPAR. Our results identify a specific E3 ubiquitin ligase that mediates degradation of a key postsynaptic regulator of synaptic morphology and function.
Ang
Xiaolu L
XL
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Seeburg
Daniel P
DP
Sheng
Morgan
M
Harper
J Wade
JW
D000818:Animals; D020690:GTPase-Activating Proteins / Q000096:biosynthesis* / Q000502:physiology; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D019089:Stem Cell Factor / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D044844:beta-Transducin Repeat-Containing Proteins / Q000378:metabolism*
D020690:GTPase-Activating Proteins; C533460:SIPA1L1 protein, human; C479629:Sipa1l1 protein, rat; D019089:Stem Cell Factor; D044844:beta-Transducin Repeat-Containing Proteins; D044767:Ubiquitin-Protein Ligases; C496126:PLK2 protein, human; D017346:Protein Serine-Threonine Kinases; C530504:Plk2 protein, rat