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A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's Disease

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Stelzl,  Ulrich
Molecular Interaction Networks (Ulrich Stelzl), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

Stroedicke,  Martin
Max Planck Society;

Worm,  Uwe
Max Planck Society;

/persons/resource/persons50138

Droege,  Anja
Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

Haenig,  Christian
Max Planck Society;

Scherzinger,  Eberhard
Max Planck Society;

Hasenbank,  Beate
Max Planck Society;

Ludewig,  Andreas H.
Max Planck Society;

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Buessow,  Konrad
Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons50409

Lehrach,  Hans
Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

Wanker,  Erich E.
Max Planck Society;

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Citation

Goehler, H., Lalowski, M., Stelzl, U., Waelter, S., Stroedicke, M., Worm, U., et al. (2004). A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's Disease. Molecular Cell, 16(6), 853-865. doi:10.1016/j.molcel.2004.09.016.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0010-87BD-F
Abstract
Analysis of protein-protein interactions (PPIs) is a valuable approach for characterizing proteins of unknown function. Here, we have developed a strategy combining library and matrix yeast two-hybrid screens to generate a highly connected PPI network for Huntington's disease (HD). The network contains 186 PPIs among 35 bait and 51 prey proteins. It revealed 165 new potential interactions, 32 of which were confirmed by independent binding experiments. The network also permitted the functional annotation of 16 uncharacterized proteins and facilitated the discovery of GIT1, a G protein-coupled receptor kinase-interacting protein, which enhances huntingtin aggregation by recruitment of the protein into membranous vesicles. Coimmunoprecipitations and immunofluorescence studies revealed that GIT1 and huntingtin associate in mammalian cells under physiological conditions. Moreover, GIT1 localizes to neuronal inclusions, and is selectively cleaved in HD brains, indicating that its distribution and function is altered during disease pathogenesis.