title: A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration.
abstract: Many human inherited neurodegenerative disorders are characterized by loss of balance due to cerebellar Purkinje cell (PC) degeneration. Although the disease-causing mutations have been identified for a number of these disorders, the normal functions of the proteins involved remain, in many cases, unknown. To gain insight into the function of proteins involved in PC degeneration, we developed an interaction network for 54 proteins involved in 23 inherited ataxias and expanded the network by incorporating literature-curated and evolutionarily conserved interactions. We identified 770 mostly novel protein-protein interactions using a stringent yeast two-hybrid screen; of 75 pairs tested, 83% of the interactions were verified in mammalian cells. Many ataxia-causing proteins share interacting partners, a subset of which have been found to modify neurodegeneration in animal models. This interactome thus provides a tool for understanding pathogenic mechanisms common for this class of neurodegenerative disorders and for identifying candidate genes for inherited ataxias.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Janghoo
authors.initials: J
authors.lastname: Lim
authors.forename: Tong
authors.initials: T
authors.lastname: Hao
authors.forename: Chad
authors.initials: C
authors.lastname: Shaw
authors.forename: Akash J
authors.initials: AJ
authors.lastname: Patel
authors.forename: Gábor
authors.initials: G
authors.lastname: Szabó
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Rual
authors.forename: C Joseph
authors.initials: CJ
authors.lastname: Fisk
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Alex
authors.initials: A
authors.lastname: Smolyar
authors.forename: David E
authors.initials: DE
authors.lastname: Hill
authors.forename: Albert-László
authors.initials: AL
authors.lastname: Barabási
authors.forename: Marc
authors.initials: M
authors.lastname: Vidal
authors.forename: Huda Y
authors.initials: HY
authors.lastname: Zoghbi
mesh_terms: D000818:Animals; D001259:Ataxia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019295:Computational Biology; D030562:Databases, Protein; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020543:Proteome; D011689:Purkinje Cells / Q000473:pathology / Q000502:physiology; D020798:Two-Hybrid System Techniques
chemical_list: D009419:Nerve Tissue Proteins; D020543:Proteome