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

Item Type:Article
Title:A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease
Creators Name:Goehler, H. and Lalowski, M. and Stelzl, U. and Waelter, S. and Stroedicke, M. and Worm, U. and Droege, A. and Lindenberg, K.S. and Knoblich, M. and Haenig, C. and Herbst, M. and Suopanki, J. and Scherzinger, E. and Abraham, C. and Bauer, B. and Hasenbank, R. and Fritzsche, A. and Ludewig, A.H. and Buessow, K. and Coleman, S.H. and Gutekunst, C.A. and Landwehrmeyer, B.G. and Lehrach, H. and Wanker, E.E.
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.
Keywords:Amino Acid Sequence, Binding Sites, COS Cells, Cell Cycle Proteins, Cercopithecus aethiops, GTPase-Activating Proteins, Glutathione, Huntington Disease, Monoclonal Antibodies, Nerve Tissue Proteins, Nuclear Proteins, PC12 Cells, Phosphoproteins, Precipitin Tests, Proline, Protein Binding, RNA Interference, Recombinant Fusion Proteins, Signal Transducing Adaptor Proteins, Tertiary Protein Structure, Tissue Distribution, Transgenic Mice
Source:Molecular Cell
ISSN:1097-2765
Publisher:Cell Press (U.S.A.)
Volume:15
Number:6
Page Range:853-865
Date:24 September 2004
Additional Information:Erratum in: Mol Cell 19(2): 287.
Official Publication:https://doi.org/10.1016/j.molcel.2004.09.016
PubMed:View item in PubMed

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