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

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

Molecular cell (2004-09-24)
Heike Goehler, Maciej Lalowski, Ulrich Stelzl, Stephanie Waelter, Martin Stroedicke, Uwe Worm, Anja Droege, Katrin S Lindenberg, Maria Knoblich, Christian Haenig, Martin Herbst, Jaana Suopanki, Eberhard Scherzinger, Claudia Abraham, Bianca Bauer, Renate Hasenbank, Anja Fritzsche, Andreas H Ludewig, Konrad Büssow, Konrad Buessow, Sarah H Coleman, Claire-Anne Gutekunst, Bernhard G Landwehrmeyer, Hans Lehrach, Erich E Wanker
PMID15383276
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.