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

Bin Ma; Jeffrey N. Savas; Man Shan Yu; Brady P. Culver; Moses V. Chao; Naoko Tanese

doi:10.1038/srep00140

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

Bin Ma, Jeffrey N. Savas, Man Shan Yu, Brady P. Culver, Moses V. Chao, Naoko Tanese^*

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

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.

Original language	English (US)
Article number	140
Journal	Scientific reports
Volume	1
DOIs	https://doi.org/10.1038/srep00140
State	Published - 2011

Funding

This work was supported by the Hereditary Disease Foundation (NT), grants from the CHDI Foundation, Inc. (NT, MVC), a grant from the NIH (NS061917 to NT), and a Shared Instrumentation Grant from the NIH (S10 RR017970). We thank Ramin Shiekhattar for the AGO2 antibody, Nobutaka Hirokawa for the anti-KIF5A and anti-KIF5C (UKHC) antibodies, Gary Bassell for the anti-ZBP1 antibody and the ZBP1 plasmid, Michael Hayden for the anti-Phos-Htt antibody, Hiroko Bannai for the NLS-MS2-Venus plasmid, Jan Ellenberg for the lN reporter system, Trina Schroer for the EGFP-DIC2, Don Arnold for the GFP-KIF5A, Thomas Meier for the MS2-RFP, and Wayne Rasband for the ImageJ program.

ASJC Scopus subject areas

General

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10.1038/srep00140

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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.",

author = "Bin Ma and Savas, {Jeffrey N.} and Yu, {Man Shan} and Culver, {Brady P.} and Chao, {Moses V.} and Naoko Tanese",

note = "Funding Information: This work was supported by the Hereditary Disease Foundation (NT), grants from the CHDI Foundation, Inc. (NT, MVC), a grant from the NIH (NS061917 to NT), and a Shared Instrumentation Grant from the NIH (S10 RR017970). We thank Ramin Shiekhattar for the AGO2 antibody, Nobutaka Hirokawa for the anti-KIF5A and anti-KIF5C (UKHC) antibodies, Gary Bassell for the anti-ZBP1 antibody and the ZBP1 plasmid, Michael Hayden for the anti-Phos-Htt antibody, Hiroko Bannai for the NLS-MS2-Venus plasmid, Jan Ellenberg for the lN reporter system, Trina Schroer for the EGFP-DIC2, Don Arnold for the GFP-KIF5A, Thomas Meier for the MS2-RFP, and Wayne Rasband for the ImageJ program.",

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doi = "10.1038/srep00140",

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journal = "Scientific reports",

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AU - Savas, Jeffrey N.

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AU - Chao, Moses V.

AU - Tanese, Naoko

N1 - Funding Information: This work was supported by the Hereditary Disease Foundation (NT), grants from the CHDI Foundation, Inc. (NT, MVC), a grant from the NIH (NS061917 to NT), and a Shared Instrumentation Grant from the NIH (S10 RR017970). We thank Ramin Shiekhattar for the AGO2 antibody, Nobutaka Hirokawa for the anti-KIF5A and anti-KIF5C (UKHC) antibodies, Gary Bassell for the anti-ZBP1 antibody and the ZBP1 plasmid, Michael Hayden for the anti-Phos-Htt antibody, Hiroko Bannai for the NLS-MS2-Venus plasmid, Jan Ellenberg for the lN reporter system, Trina Schroer for the EGFP-DIC2, Don Arnold for the GFP-KIF5A, Thomas Meier for the MS2-RFP, and Wayne Rasband for the ImageJ program.

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

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

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