Network organization of the huntingtin proteomic interactome in mammalian brain

Academic Article

Abstract

  • We used affinity-purification mass spectrometry to identify 747 candidate proteins that are complexed with Huntingtin (Htt) in distinct brain regions and ages in Huntington's disease (HD) and wild-type mouse brains. To gain a systems-level view of the Htt interactome, we applied Weighted Correlation Network Analysis to the entire proteomic data set to unveil a verifiable rank of Htt-correlated proteins and a network of Htt-interacting protein modules, with each module highlighting distinct aspects of Htt biology. Importantly, the Htt-containing module is highly enriched with proteins involved in 14-3-3 signaling, microtubule-based transport, and proteostasis. Top-ranked proteins in this module were validated as Htt interactors and genetic modifiers in an HD Drosophila model. Our study provides a compendium of spatiotemporal Htt-interacting proteins in the mammalian brain and presents an approach for analyzing proteomic interactome data sets to build in vivo protein networks in complex tissues, such as the brain. © 2012 Elsevier Inc.
  • Authors

    Published In

  • Neuron  Journal
  • Digital Object Identifier (doi)

    Author List

  • Shirasaki DI; Greiner ER; Al-Ramahi I; Gray M; Boontheung P; Geschwind DH; Botas J; Coppola G; Horvath S; Loo JA
  • Start Page

  • 41
  • End Page

  • 57
  • Volume

  • 75
  • Issue

  • 1