A Protein Interaction Network Links GIT1, an Enhancer of Huntingtin Aggregation, to Huntington’s Disease

Goehler, Heike; Łałowski, 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, Renate; Fritzsche, Anja; Ludewig, Andreas H.; Buessow, K.; Coleman, Sarah H.; Gutekunst, Claire‐Anne; Landwehrmeyer, Bernhard; Lehrach, Hans; Wanker, Erich E.

doi:10.1016/j.molcel.2005.06.031

Cited by 33 publications

(39 citation statements)

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“…Saccharomyces cerevisiae L40ccU A ( Mat a , His3∆200 , trp1‐901 , leu2‐3 , 112 , lys2:(lexAop) 4 ‐HIS3 , ura3::(lexAop) 8 –lacZ , ADE::(lexAop) 8 ‐URA , GAL4 , ga180 , can1 , cyh2) Goehler et al ., . Escherichia coli DB3.1 (F‐ , gyrA462 , endA1 , ∆(sr1‐recA) mcrB , mrr , hsdS20(rB‐mB) , supE44 , ara14 , galK2 , lacY1 , proA2 , rpsL20(Smr) , xy15 , ∆leu , mt11) .…”

Section: Methodsmentioning

confidence: 99%

The sucrose transporter SlSUT2 from tomato interacts with brassinosteroid functioning and affects arbuscular mycorrhiza formation

et al. 2014

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SUMMARYMycorrhizal plants benefit from the fungal partners by getting better access to soil nutrients. In exchange, the plant supplies carbohydrates to the fungus. The additional carbohydrate demand in mycorrhizal plants was shown to be balanced partially by higher CO 2 assimilation and increased C metabolism in shoots and roots. In order to test the role of sucrose transport for fungal development in arbuscular mycorrhizal (AM) tomato, transgenic plants with down-regulated expression of three sucrose transporter genes were analysed. Plants that carried an antisense construct of SlSUT2 (SlSUT2as) repeatedly exhibited increased mycorrhizal colonization and the positive effect of plants to mycorrhiza was abolished. Grafting experiments between transgenic and wild-type rootstocks and scions indicated that mainly the root-specific function of SlSUT2 has an impact on colonization of tomato roots with the AM fungus. Localization of SISUT2 to the periarbuscular membrane indicates a role in back transport of sucrose from the periarbuscular matrix into the plant cell thereby affecting hyphal development. Screening of an expression library for SlSUT2-interacting proteins revealed interactions with candidates involved in brassinosteroid (BR) signaling or biosynthesis. Interaction of these candidates with SlSUT2 was confirmed by bimolecular fluorescence complementation. Tomato mutants defective in BR biosynthesis were analysed with respect to mycorrhizal symbiosis and showed indeed decreased mycorrhization. This finding suggests that BRs affect mycorrhizal infection and colonization. If the inhibitory effect of SlSUT2 on mycorrhizal growth involves components of BR synthesis and of the BR signaling pathway is discussed.

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Section: Methodsmentioning

confidence: 99%

The sucrose transporter SlSUT2 from tomato interacts with brassinosteroid functioning and affects arbuscular mycorrhiza formation

et al. 2014

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“…Interactions were detected by assaying the simultaneous activation of the (lexAop)4‐HIS3 and (lexAop)8‐URA3 reporter genes on SDIV selection medium. The activity of the (lexAop)8‐lacZ reporter was measured using a ß‐galactosidase assay after growth on SDIV agar in an additional experiment [19].…”

Section: Methodsmentioning

confidence: 99%

The collapsin response mediator protein 1 (CRMP‐1) and the promyelocytic leukemia zinc finger protein (PLZF) bind to UDP‐N‐acetylglucosamine 2‐epimerase/N‐acetylmannosamine kinase (GNE), the key enzyme of sialic acid biosynthesis

et al. 2006

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Sialic acids (Sia) are expressed as terminal sugars in many glycoconjugates. They are involved in a variety of cell-cell interactions and therefore play an important role during development and regeneration. UDP-N-acetylglucosamine 2-epimerase/ N-acetylmannosamine kinase (GNE) is the key enzyme in the de novo synthesis of Sia and it is a regulator of cell surface sialylation. Inactivation of GNE in mice results in early embryonic lethality. Mutations in the GNE gene are of clinical relevance in hereditary inclusion body myopathy, but these mutations do not necessarily decrease the enzymatic activity of GNE. In this study, we searched for novel function of the GNE protein beside its enzymatic function in the Sia biosynthesis. We here report the identification of novel GNE-interacting proteins. Using a human prey matrix we identified four proteins interacting with GNE in a yeast two-hybrid assay. For two of them, the collapsin response mediator protein 1 and the promyelocytic leukemia zinc finger protein, we could verify protein-protein interaction with GNE.

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“…To evaluate the quality of the Y2H data, a representative sample of interactions was randomly selected for verification assays because interactions recapitulated independently are unlikely to be experimental false positives (Goehler et al, 2004). Using a membrane coimmunoprecipitation assay (Figure 2A), 116 protein pairs were tested with a success rate of 72/116 (62%).…”

Section: Experimental Verification Of Interactionsmentioning

confidence: 99%

“…Taking into account the high potential of human PPIs for understanding disease mechanisms and signaling cascades, smaller scale, more specific interaction maps have been generated. Examples are an interaction network for Huntington's disease with 186 interactions (Goehler et al, 2004) or a network for the transforming growth factor-β (TGF-β) signaling pathway with 755 interactions (Colland et al, 2004). In addition, bioinformatic analyses have been performed, collecting information on human interactions from hypothesis-driven studies (Peri et al, 2003) or from studies identifying conserved orthologous interactions (Lehner and Fraser, 2004), which are referred to as "interologs" (Matthews et al, 2001;Walhout et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

A Human Protein-Protein Interaction Network: A Resource for Annotating the Proteome

Stelzl

Worm

Łałowski

et al. 2005

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Protein-protein interaction maps provide a valuable framework for a better understanding of the functional organization of the proteome. To detect interacting pairs of human proteins systematically, a protein matrix of 4456 baits and 5632 preys was screened by automated yeast two-hybrid (Y2H) interaction mating. We identified 3186 mostly novel interactions among 1705 proteins, resulting in a large, highly connected network. Independent pull-down and co-immunoprecipitation assays validated the overall quality of the Y2H interactions. Using topological and GO criteria, a scoring system was developed to define 911 high-confidence interactions among 401 proteins. Furthermore, the network was searched for interactions linking uncharacterized gene products and human disease proteins to regulatory cellular pathways. Two novel Axin-1 interactions were validated experimentally, characterizing ANP32A and CRMP1 as modulators of Wnt signaling. Systematic human protein interaction screens can lead to a more comprehensive understanding of protein function and cellular processes.

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A Protein Interaction Network Links GIT1, an Enhancer of Huntingtin Aggregation, to Huntington’s Disease

Cited by 33 publications

References 0 publications

The sucrose transporter SlSUT2 from tomato interacts with brassinosteroid functioning and affects arbuscular mycorrhiza formation

The sucrose transporter SlSUT2 from tomato interacts with brassinosteroid functioning and affects arbuscular mycorrhiza formation

The collapsin response mediator protein 1 (CRMP‐1) and the promyelocytic leukemia zinc finger protein (PLZF) bind to UDP‐N‐acetylglucosamine 2‐epimerase/N‐acetylmannosamine kinase (GNE), the key enzyme of sialic acid biosynthesis

A Human Protein-Protein Interaction Network: A Resource for Annotating the Proteome

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