Departmental Papers (Department of Systems Pharmacology and Translational Therapeutics)

Document Type

Technical Report

Date of this Version

2009

Publication Source

PLOS Biology

Volume

7

Issue

4

DOI

10.1371/journal.pbio.1000083

Abstract

Precise neuronal networks underlie normal brain function and require distinct classes of synaptic connections. Althought 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 MRCKγ can modulate maturaion 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/Permission Statement

© 2009 Heintz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Comments

At the time of this publication, Dr. Heller was affiliated with The Rockefeller University, but she is now a faculty member at the University of Pennsylvania.

 

Date Posted:22 January 2018

This document has been peer reviewed.