ArticleThe Journal of biological chemistry2014
A large scale Huntingtin protein interaction network implicates Rho GTPase signaling pathways in Huntington disease.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 2 of them syntheses that pooled it.
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Who cites it
49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 104 citations in OpenAlex.
- Pooled it
- Meta-analysis of transcriptomic changes in optic nerve injury and neurodegenerative models reveals a fundamental response to injury throughout the central nervous system.Molecular vision · 2017Pooled it
- Huntingtin (HTT) interactome in regulation of DNA repair/remodeling and RNA processing pathways.Life science alliance · 2026Article
- Phosphoproteomics unveils the signaling dynamics in neuronal cells stimulated with insulin and insulin-like growth factors.Cell communication and signaling : CCS · 2025Article
- Structure of the Huntingtin F-actin complex reveals its role in cytoskeleton organization.Science advances · 2025Article
- Developmental and physiological impacts of pathogenic human huntingtin protein in the nervous system.Neurobiology of disease · 2024Article
- Therapeutic approaches targeting aging and cellular senescence in Huntington's disease.CNS neuroscience & therapeutics · 2024Review
- ProteinCoLoc streamlines Bayesian analysis of colocalization in microscopic images.Scientific reports · 2024Article
- Toxic effects of mutant huntingtin in axons are mediated by its proline-rich domain.Brain : a journal of neurology · 2024Article
- HAP40 modulates mutant Huntingtin aggregation and toxicity in Huntington's disease mice.Cell death & disease · 2024Article
- Roles of Rac1-Dependent Intrinsic Forgetting in Memory-Related Brain Disorders: Demon or Angel.International journal of molecular sciences · 2023Review
- Characterization of huntingtin interactomes and their dynamic responses in living cells by proximity proteomics.Journal of neurochemistry · 2023Article
- The Metabolic Basis for Nervous System Dysfunction in Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease.Current neurovascular research · 2023Article
- Huntingtin and Other Neurodegeneration-Associated Proteins in the Development of Intracellular Pathologies: Potential Target Search for Therapeutic Intervention.International journal of molecular sciences · 2022Review
- Decreased FAK activity and focal adhesion dynamics impair proper neurite formation of medium spiny neurons in Huntington's disease.Acta neuropathologica · 2022Article
- HAP40 is a conserved central regulator of Huntingtin and a potential modulator of Huntington's disease pathogenesis.PLoS genetics · 2022Article
- Huntingtin Co-Isolates with Small Extracellular Vesicles from Blood Plasma of TgHD and KI-HD Pig Models of Huntington's Disease and Human Blood Plasma.International journal of molecular sciences · 2022Article
- Dynamics of huntingtin protein interactions in the striatum identifies candidate modifiers of Huntington disease.Cell systems · 2022Article
- A Progressive Loss of phosphoSer138-Profilin Aligns with Symptomatic Course in the R6/2 Mouse Model of Huntington's Disease: Possible Sex-Dependent Signaling.Cellular and molecular neurobiology · 2022Article
- Mutant Huntingtin Protein Interaction Map Implicates Dysregulation of Multiple Cellular Pathways in Neurodegeneration of Huntington's Disease.Journal of Huntington's disease · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Huntington disease (HD) is an inherited neurodegenerative disease caused by a CAG expansion in the HTT gene. Using yeast two-hybrid methods, we identified a large set of proteins that interact with huntingtin (HTT)-interacting proteins. This network, composed of HTT-interacting proteins (HIPs) and proteins interacting with these primary nodes, contains 3235 interactions among 2141 highly interconnected proteins. Analysis of functional annotations of these proteins indicates that primary and secondary HIPs are enriched in pathways implicated in HD, including mammalian target of rapamycin, Rho GTPase signaling, and oxidative stress response. To validate roles for HIPs in mutant HTT toxicity, we show that the Rho GTPase signaling components, BAIAP2, EZR, PIK3R1, PAK2, and RAC1, are modifiers of mutant HTT toxicity. We also demonstrate that Htt co-localizes with BAIAP2 in filopodia and that mutant HTT interferes with filopodial dynamics. These data indicate that HTT is involved directly in membrane dynamics, cell attachment, and motility. Furthermore, they implicate dysregulation in these pathways as pathological mechanisms in HD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.