Journal
PLOS BIOLOGY
Volume 7, Issue 4, Pages 948-957Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.1000083
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Funding
- Human Frontier Science Program Organization
- The Rockefeller University Women and Science Fellowship [CEN5300379]
- Simons Foundation
- National Institutes of Health [RR00862, RR02220]
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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 MRCK gamma, are major unrecognized components of this synapse type. We demonstrate that MRCK gamma 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.
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