A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration.
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.
Lim
Janghoo
J
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Hao
Tong
T
Shaw
Chad
C
Patel
Akash J
AJ
Szabó
Gábor
G
Rual
Jean-François
JF
Fisk
C Joseph
CJ
Li
Ning
N
Smolyar
Alex
A
Hill
David E
DE
Barabási
Albert-László
AL
Vidal
Marc
M
Zoghbi
Huda Y
HY
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
D009419:Nerve Tissue Proteins; D020543:Proteome