title: Lissencephaly-1 promotes the recruitment of dynein and dynactin to transported mRNAs.
abstract: Microtubule-based transport mediates the sorting and dispersal of many cellular components and pathogens. However, the mechanisms by which motor complexes are recruited to and regulated on different cargos remain poorly understood. Here we describe a large-scale biochemical screen for novel factors associated with RNA localization signals mediating minus end-directed mRNA transport during Drosophila development. We identified the protein Lissencephaly-1 (Lis1) and found that minus-end travel distances of localizing transcripts are dramatically reduced in lis1 mutant embryos. Surprisingly, given its well-documented role in regulating dynein mechanochemistry, we uncovered an important requirement for Lis1 in promoting the recruitment of dynein and its accessory complex dynactin to RNA localization complexes. Furthermore, we provide evidence that Lis1 levels regulate the overall association of dynein with dynactin. Our data therefore reveal a critical role for Lis1 within the mRNA localization machinery and suggest a model in which Lis1 facilitates motor complex association with cargos by promoting the interaction of dynein with dynactin.
authors.affiliation: Cell Biology Division, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, England, UK.
authors.forename: Carly I
authors.initials: CI
authors.lastname: Dix
authors.forename: Harish Chandra
authors.initials: HC
authors.lastname: Soundararajan
authors.forename: Nikola S
authors.initials: NS
authors.lastname: Dzhindzhev
authors.forename: Farida
authors.initials: F
authors.lastname: Begum
authors.forename: Beat
authors.initials: B
authors.lastname: Suter
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohkura
authors.forename: Elaine
authors.initials: E
authors.lastname: Stephens
authors.forename: Simon L
authors.initials: SL
authors.lastname: Bullock
mesh_terms: D000818:Animals; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D021381:Protein Transport; D034443:RNA Transport; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D000072159:Dynactin Complex; C513192:Lis-1 protein, Drosophila; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D004398:Dyneins
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