Proteomic studies of a single cns synapse type: The parallel fiber/Purkinje cell synapse

Fekrije Selimi, Ileana M. Cristea, Elizabeth Heller, Brian T. Chait, Nathaniel Heintz

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Precise neuronal networks underlie normal brain function and require distinct classes of synaptic connections. Although it has been shown that certain individual proteins can localize to different classes of synapses, the biochemical composition of specific synapse types is not known. Here, we have used a combination of genetically engineered mice, affinity purification, and mass spectrometry to profile proteins at parallel fiber/Purkinje cell synapses. We identify approximately 60 candidate postsynaptic proteins that can be classified into 11 functional categories. Proteins involved in phospholipid metabolism and signaling, such as the protein kinase MRCKγ, are major unrecognized components of this synapse type. We demonstrate that MRCKc can modulate maturation of dendritic spines in cultured cortical neurons, and that it is localized specifically to parallel fiber/Purkinje cell synapses in vivo. Our data identify a novel synapse-specific signaling pathway, and provide an approach for detailed investigations of the biochemical complexity of central nervous system synapse types. Copyright:

Original languageEnglish (US)
Pages (from-to)948-957
Number of pages10
JournalPLoS biology
Volume7
Issue number4
DOIs
StatePublished - Apr 2009

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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