Nuclear-localized Asunder regulates cytoplasmic dynein localization via its role in the Integrator complex

Jeanne N. Jodoin, Poojitha Sitaram, Todd R. Albrecht, Sarah B. May, Mohammad Shboul, Ethan Lee, Bruno Reversade, Eric Wagner, Laura A. Lee

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

We previously reported that Asunder (ASUN) is essential for recruitment of dynein motors to the nuclear envelope (NE) and nucleus-centrosome coupling at the onset of cell division in cultured human cells and Drosophila spermatocytes, although the mechanisms underlying this regulation remain unknown. We also identified ASUN as a functional component of Integrator (INT), a multisubunit complex required for 3'-end processing of small nuclear RNAs. We now provide evidence that ASUN acts in the nucleus in concert with other INT components to mediate recruitment of dynein to the NE. Knockdown of other individual INT subunits in HeLa cells recapitulates the loss of perinuclear dynein in ASUN-small interfering RNA cells. Forced localization of ASUN to the cytoplasm via mutation of its nuclear localization sequence blocks its capacity to restore perinuclear dynein in both cultured human cells lacking ASUN and Drosophila asun spermatocytes. In addition, the levels of several INT subunits are reduced at G2/M when dynein is recruited to the NE, suggesting that INT does not directly mediate this step. Taken together, our data support a model in which a nuclear INT complex promotes recruitment of cytoplasmic dynein to the NE, possibly via a mechanism involving RNA processing.

Original languageEnglish (US)
Pages (from-to)2954-2965
Number of pages12
JournalMolecular Biology of the Cell
Volume24
Issue number18
DOIs
StatePublished - Sep 15 2013
Externally publishedYes

Fingerprint

Cytoplasmic Dyneins
Dyneins
Nuclear Envelope
Spermatocytes
Drosophila
Cultured Cells
Small Nuclear RNA
Centrosome
HeLa Cells
Cell Division
Small Interfering RNA
Cytoplasm
RNA
Mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Jodoin, J. N., Sitaram, P., Albrecht, T. R., May, S. B., Shboul, M., Lee, E., ... Lee, L. A. (2013). Nuclear-localized Asunder regulates cytoplasmic dynein localization via its role in the Integrator complex. Molecular Biology of the Cell, 24(18), 2954-2965. https://doi.org/10.1091/mbc.E13-05-0254

Nuclear-localized Asunder regulates cytoplasmic dynein localization via its role in the Integrator complex. / Jodoin, Jeanne N.; Sitaram, Poojitha; Albrecht, Todd R.; May, Sarah B.; Shboul, Mohammad; Lee, Ethan; Reversade, Bruno; Wagner, Eric; Lee, Laura A.

In: Molecular Biology of the Cell, Vol. 24, No. 18, 15.09.2013, p. 2954-2965.

Research output: Contribution to journalArticle

Jodoin, JN, Sitaram, P, Albrecht, TR, May, SB, Shboul, M, Lee, E, Reversade, B, Wagner, E & Lee, LA 2013, 'Nuclear-localized Asunder regulates cytoplasmic dynein localization via its role in the Integrator complex', Molecular Biology of the Cell, vol. 24, no. 18, pp. 2954-2965. https://doi.org/10.1091/mbc.E13-05-0254
Jodoin, Jeanne N. ; Sitaram, Poojitha ; Albrecht, Todd R. ; May, Sarah B. ; Shboul, Mohammad ; Lee, Ethan ; Reversade, Bruno ; Wagner, Eric ; Lee, Laura A. / Nuclear-localized Asunder regulates cytoplasmic dynein localization via its role in the Integrator complex. In: Molecular Biology of the Cell. 2013 ; Vol. 24, No. 18. pp. 2954-2965.
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