6533b7ddfe1ef96bd1274ac0

RESEARCH PRODUCT

Huntingtin mediates dendritic transport of β-actin mRNA in rat neurons

Moses V. ChaoJeffrey N. SavasJeffrey N. SavasBin MaBin MaNaoko TaneseMan-shan YuBrady P. Culver

subject

congenital hereditary and neonatal diseases and abnormalitiesHuntingtinDyneinModels NeurologicalBiological Transport ActiveKinesinsRNA-binding proteinNerve Tissue Proteinsmacromolecular substancesBiologyCytoplasmic GranulesMicrotubulesArticle03 medical and health sciences0302 clinical medicineMicrotubulemental disordersProtein biosynthesisMRNA transportAnimalsRNA MessengerRNA Small InterferingRats WistarCells Cultured030304 developmental biologyNeurons0303 health sciencesHuntingtin ProteinMultidisciplinaryMolecular Motor ProteinsBrainDyneinsNuclear ProteinsRNA-Binding ProteinsDendritesActinsCell biologynervous system diseasesRatsDendritic transportnervous systemGene Knockdown TechniquesKinesinFemale030217 neurology & neurosurgerySignal Transduction

description

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.

10.1038/srep00140http://europepmc.org/articles/PMC3216621