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

Jodoin JN, Sitaram P, Albrecht TR, May SB, Shboul M, Lee E, Reversade B, Wagner EJ, Lee LA
Mol Biol Cell. 2013 24 (18): 2954-65

PMID: 23904267 · PMCID: PMC3771956 · DOI:10.1091/mbc.E13-05-0254

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.

MeSH Terms (22)

Amino Acid Sequence Animals Carrier Proteins Cell Cycle Proteins Cell Division Cell Nucleus Cytoplasmic Dyneins Drosophila melanogaster Drosophila Proteins G2 Phase HeLa Cells Humans Male Molecular Sequence Data Multiprotein Complexes Nuclear Envelope Nuclear Localization Signals Protein Subunits Protein Transport RNA, Small Interfering Spermatocytes Subcellular Fractions

Connections (1)

This publication is referenced by other Labnodes entities: