title: Nuclear-localized Asunder regulates cytoplasmic dynein localization via its role in the integrator complex.
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.
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232-8240 Department of Biochemistry and Molecular Biology, University of Texas Medical School at Houston, Houston, TX 77030 Institute of Medical Biology, A*STAR, Singapore 138648 Department of Pediatrics, National University of Singapore, Singapore 119228.
authors.forename: Jeanne N
authors.initials: JN
authors.lastname: Jodoin
authors.forename: Poojitha
authors.initials: P
authors.lastname: Sitaram
authors.forename: Todd R
authors.initials: TR
authors.lastname: Albrecht
authors.forename: Sarah B
authors.initials: SB
authors.lastname: May
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shboul
authors.forename: Ethan
authors.initials: E
authors.lastname: Lee
authors.forename: Bruno
authors.initials: B
authors.lastname: Reversade
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Wagner
authors.forename: Laura A
authors.initials: LA
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism*; D056445:Cytoplasmic Dyneins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D016195:G2 Phase; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism; D019913:Nuclear Localization Signals / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism; D013090:Spermatocytes / Q000166:cytology / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C581358:INTS13 protein, human; D046912:Multiprotein Complexes; D019913:Nuclear Localization Signals; D021122:Protein Subunits; D034741:RNA, Small Interfering; C544294:asun protein, Drosophila; D056445:Cytoplasmic Dyneins
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