title: Fragile X protein functions with lgl and the par complex in flies and mice.
abstract: Fragile X syndrome, the most common form of inherited mental retardation, is caused by loss of function for the Fragile X Mental Retardation 1 gene (FMR1). FMR1 protein (FMRP) has specific mRNA targets and is thought to be involved in their transport to subsynaptic sites as well as translation regulation. We report a saturating genetic screen of the Drosophila autosomal genome to identify functional partners of dFmr1. We recovered 19 mutations in the tumor suppressor lethal (2) giant larvae (dlgl) gene and 90 mutations at other loci. dlgl encodes a cytoskeletal protein involved in cellular polarity and cytoplasmic transport and is regulated by the PAR complex through phosphorylation. We provide direct evidence for a Fmrp/Lgl/mRNA complex, which functions in neural development in flies and is developmentally regulated in mice. Our data suggest that Lgl may regulate Fmrp/mRNA sorting, transport, and anchoring via the PAR complex.
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Daniela C
authors.initials: DC
authors.lastname: Zarnescu
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.forename: Joerg
authors.initials: J
authors.lastname: Betschinger
authors.forename: Mika
authors.initials: M
authors.lastname: Nakamoto
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Dockendorff
authors.forename: Yue
authors.initials: Y
authors.lastname: Feng
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Jongens
authors.forename: John C
authors.initials: JC
authors.lastname: Sisson
authors.forename: Juergen A
authors.initials: JA
authors.lastname: Knoblich
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Warren
authors.forename: Kevin
authors.initials: K
authors.lastname: Moses
mesh_terms: D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002458:Cell Fractionation / Q000379:methods; D002478:Cells, Cultured; D003001:Cloning, Molecular / Q000379:methods; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D005123:Eye / Q000473:pathology / Q000648:ultrastructure; D051860:Fragile X Messenger Ribonucleoprotein 1; D018507:Gene Expression Regulation, Developmental; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008855:Microscopy, Electron, Scanning / Q000379:methods; D016296:Mutagenesis; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology*; D012160:Retina / Q000473:pathology / Q000648:ultrastructure; D013347:Subcellular Fractions / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D000429:Alcohol Oxidoreductases; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C467328:FMR1 protein, Drosophila; C497683:FMR1 protein, human; C497684:Fmr1 protein, mouse; C081435:l(2)gl protein, Drosophila; C110191:phenylacetaldehyde reductase