Regulation of postsynaptic RapGAP SPAR by polo-like kinase 2 and the SCFβ-TRCP ubiquitin ligase in hippocampal neurons

Xiaolu L. Ang, Daniel P. Seeburg, Morgan Sheng, J. Wade Harper

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

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 SCFβ-TRCP complex, a multisubunit E3 ubiquitin ligase, targets the postsynaptic spine-associated Rap GTPase activating protein (SPAR) for degradation in neurons. SPAR degradation by SCFβ-TRCP depended on the activity-inducible protein kinase Polo-like kinase 2 (Plk2). In the presence of Plk2, SPAR physically associated with the SCFβ-TRCP complex through a canonical phosphodegron. In hippocampal neurons, disruption of the SCFβ-TRCP complex by overexpression of dominant interfering β-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.

Original languageEnglish (US)
Pages (from-to)29424-29432
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number43
DOIs
StatePublished - Oct 24 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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