Network organization of the huntingtin proteomic interactome in mammalian brain

Neuron. 2012 Jul 12;75(1):41-57. doi: 10.1016/j.neuron.2012.05.024.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain / physiology
  • Disease Models, Animal*
  • Drosophila
  • Female
  • Gene Regulatory Networks / genetics*
  • Humans
  • Huntingtin Protein
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism*
  • Proteomics / methods*


  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins