title: Genetic circuitry of Survival motor neuron, the gene underlying spinal muscular atrophy.
abstract: The clinical severity of the neurodegenerative disorder spinal muscular atrophy (SMA) is dependent on the levels of functional Survival Motor Neuron (SMN) protein. Consequently, current strategies for developing treatments for SMA generally focus on augmenting SMN levels. To identify additional potential therapeutic avenues and achieve a greater understanding of SMN, we applied in vivo, in vitro, and in silico approaches to identify genetic and biochemical interactors of the Drosophila SMN homolog. We identified more than 300 candidate genes that alter an Smn-dependent phenotype in vivo. Integrating the results from our genetic screens, large-scale protein interaction studies, and bioinformatic analysis, we define a unique interactome for SMN that provides a knowledge base for a better understanding of SMA.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Anindya
authors.initials: A
authors.lastname: Sen
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Dimlich
authors.forename: K G
authors.initials: KG
authors.lastname: Guruharsha
authors.forename: Mark W
authors.initials: MW
authors.lastname: Kankel
authors.forename: Kazuya
authors.initials: K
authors.lastname: Hori
authors.forename: Takakazu
authors.initials: T
authors.lastname: Yokokura
authors.forename: Sophie
authors.initials: S
authors.lastname: Brachat
authors.forename: Delwood
authors.initials: D
authors.lastname: Richardson
authors.forename: Joseph
authors.initials: J
authors.lastname: Loureiro
authors.forename: Rajeev
authors.initials: R
authors.lastname: Sivasankaran
authors.forename: Daniel
authors.initials: D
authors.lastname: Curtis
authors.forename: Lance S
authors.initials: LS
authors.lastname: Davidow
authors.forename: Lee L
authors.initials: LL
authors.lastname: Rubin
authors.forename: Anne C
authors.initials: AC
authors.lastname: Hart
authors.forename: David
authors.initials: D
authors.lastname: Van Vactor
authors.forename: Spyros
authors.initials: S
authors.lastname: Artavanis-Tsakonas
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000235:genetics*; D053263:Gene Regulatory Networks; D017344:Genes, Insect; D006801:Humans; D051188:Knowledge Bases; D009469:Neuromuscular Junction / Q000235:genetics; D010641:Phenotype; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics*; D013045:Species Specificity; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D016601:RNA-Binding Proteins; C542563:Smn protein, Drosophila
keywords: ALS; disease model; neurodegeneration; neuromuscular junction; proteomics