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          Institute: MPI für molekulare Genetik     Collection: Department of Vertebrate Genomics     Display Documents

ID: 230207.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's Disease
Authors:Goehler, Heike; Lalowski, Maciej; Stelzl, Ulrich; Waelter, Stephanie; Stroedicke, Martin; Worm, Uwe; Droege, Anja; Lindenberg, Katrin S.; Knoblich, Maria; Haenig, Christian; Herbst, Martin; Suopanki, Jaana; Scherzinger, Eberhard; Abraham, Claudia; Bauer, Bianca; Hasenbank, Beate; Fritzsche, Anja; Ludewig, Andreas H.; Buessow, Konrad; Coleman, Sarah H.; Gutekunst, Claire-Anne; Landwehrmeyer, Bernhard G.; Lehrach, Hans; Wanker, Erich E.
Date of Publication (YYYY-MM-DD):2004-09-24
Title of Journal:Molecular Cell
Journal Abbrev.:Mol Cell
Issue / Number:6
Start Page:853
End Page:865
Copyright:© 2004 Cell Press
Review Status:not specified
Audience:Experts Only
Abstract / Description: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.
Comment of the Author/Creator:Published online: 2004-09-23
External Publication Status:published
Document Type:Article
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:Max-Delbrueck-Center for Molecular Medicine, 13125, Berlin-Buch, Germany;
Department of Neurology, University of Ulm, 89075, Ulm, Germany;
Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA
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