title: Huntingtin mediates dendritic transport of β-actin mRNA in rat neurons.
abstract: Transport of mRNAs to diverse neuronal locations via RNA granules serves an important function in regulating protein synthesis within restricted sub-cellular domains. We recently detected the Huntington's disease protein huntingtin (Htt) in dendritic RNA granules; however, the functional significance of this localization is not known. Here we report that Htt and the huntingtin-associated protein 1 (HAP1) are co-localized with the microtubule motor proteins, the KIF5A kinesin and dynein, during dendritic transport of β-actin mRNA. Live cell imaging demonstrated that β-actin mRNA is associated with Htt, HAP1, and dynein intermediate chain in cultured neurons. Reduction in the levels of Htt, HAP1, KIF5A, and dynein heavy chain by lentiviral-based shRNAs resulted in a reduction in the transport of β-actin mRNA. These findings support a role for Htt in participating in the mRNA transport machinery that also contains HAP1, KIF5A, and dynein.
authors.affiliation: Department of Microbiology, New York University School of Medicine, 550 First Ave., New York, NY 10016, USA; Institute of Pathology, University Medical Center, Johannes Gutenberg University, Langenbeckstrasse 1, D-55101 Mainz, Germany.
authors.forename: Bin
authors.initials: B
authors.lastname: Ma
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Savas
authors.forename: Man-Shan
authors.initials: MS
authors.lastname: Yu
authors.forename: Brady P
authors.initials: BP
authors.lastname: Culver
authors.forename: Moses V
authors.initials: MV
authors.lastname: Chao
authors.forename: Naoko
authors.initials: N
authors.lastname: Tanese
mesh_terms: D000199:Actins / Q000235:genetics*; D000818:Animals; D001693:Biological Transport, Active; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D004398:Dyneins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D000071058:Huntingtin Protein; D016547:Kinesins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008959:Models, Neurological; D020409:Molecular Motor Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
chemical_list: D000199:Actins; C490757:Hap1 protein, rat; C499524:Htt protein, rat; D000071058:Huntingtin Protein; C498634:Igf2bp1 protein, rat; D020409:Molecular Motor Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C547919:Kif5A protein, rat; D004398:Dyneins; D016547:Kinesins