Transportin acts to regulate mitotic assembly events by target binding rather than Ran sequestration.

Abstract:

:The nuclear import receptors importin β and transportin play a different role in mitosis: both act phenotypically as spatial regulators to ensure that mitotic spindle, nuclear membrane, and nuclear pore assembly occur exclusively around chromatin. Importin β is known to act by repressing assembly factors in regions distant from chromatin, whereas RanGTP produced on chromatin frees factors from importin β for localized assembly. The mechanism of transportin regulation was unknown. Diametrically opposed models for transportin action are as follows: 1) indirect action by RanGTP sequestration, thus down-regulating release of assembly factors from importin β, and 2) direct action by transportin binding and inhibiting assembly factors. Experiments in Xenopus assembly extracts with M9M, a superaffinity nuclear localization sequence that displaces cargoes bound by transportin, or TLB, a mutant transportin that can bind cargo and RanGTP simultaneously, support direct inhibition. Consistently, simple addition of M9M to mitotic cytosol induces microtubule aster assembly. ELYS and the nucleoporin 107-160 complex, components of mitotic kinetochores and nuclear pores, are blocked from binding to kinetochores in vitro by transportin, a block reversible by M9M. In vivo, 30% of M9M-transfected cells have spindle/cytokinesis defects. We conclude that the cell contains importin β and transportin "global positioning system"or "GPS" pathways that are mechanistically parallel.

journal_name

Mol Biol Cell

authors

Bernis C,Swift-Taylor B,Nord M,Carmona S,Chook YM,Forbes DJ

doi

10.1091/mbc.E13-08-0506

subject

Has Abstract

pub_date

2014-04-01 00:00:00

pages

992-1009

issue

7

eissn

1059-1524

issn

1939-4586

pii

mbc.E13-08-0506

journal_volume

25

pub_type

杂志文章
  • Pho4 mediates phosphate acquisition in Candida albicans and is vital for stress resistance and metal homeostasis.

    abstract::During interactions with its mammalian host, the pathogenic yeast Candida albicans is exposed to a range of stresses such as superoxide radicals and cationic fluxes. Unexpectedly, a nonbiased screen of transcription factor deletion mutants revealed that the phosphate-responsive transcription factor Pho4 is vital for t...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-05-0266

    authors: Ikeh MA,Kastora SL,Day AM,Herrero-de-Dios CM,Tarrant E,Waldron KJ,Banks AP,Bain JM,Lydall D,Veal EA,MacCallum DM,Erwig LP,Brown AJ,Quinn J

    更新日期:2016-09-01 00:00:00

  • Transforming growth factor beta 1 (TGF beta 1) reduces cellular levels of p34cdc2, and this effect is abrogated by adenovirus independently of the E1A-associated pRB binding activity.

    abstract::We have used E1A probes to study the roles of the p34cdc2 kinase and the retinoblastoma tumor susceptibility gene product (pRB) in transforming growth factor beta 1 (TGF beta 1)-mediated growth suppression in mink lung epithelial (Mv1Lu) cells. In agreement with previous reports, we see a decline in p34cdc2 kinase act...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.3.6.655

    authors: Abraham SE,Carter MC,Moran E

    更新日期:1992-06-01 00:00:00

  • ER membrane protein complex is required for the insertions of late-synthesized transmembrane helices of Rh1 in Drosophila photoreceptors.

    abstract::Most membrane proteins are synthesized on and inserted into the membrane of the endoplasmic reticulum (ER), in eukaryote. The widely conserved ER membrane protein complex (EMC) facilitates the biogenesis of a wide range of membrane proteins. In this study, we investigated the EMC function using Drosophila photorecepto...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E19-08-0434

    authors: Hiramatsu N,Tago T,Satoh T,Satoh AK

    更新日期:2019-11-01 00:00:00

  • Unique suppression of prostaglandin H synthase-2 expression by inhibition of histone deacetylation, specifically in human amnion but not adjacent choriodecidua.

    abstract::The key molecular regulatory mechanisms that govern and coordinate the molecular alterations that underpin the process of human labor remain incompletely understood although enhanced intrauterine prostaglandin production is known to be requisite. Studies from cancer tissues have indicated that at least one key enzyme ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-08-0818

    authors: Mitchell MD

    更新日期:2006-01-01 00:00:00

  • The lipid binding pleckstrin homology domain in UNC-104 kinesin is necessary for synaptic vesicle transport in Caenorhabditis elegans.

    abstract::UNC-104 (KIF1A) is a kinesin motor that transports synaptic vesicles from the neuronal cell body to the terminal. Previous in vitro studies have shown that a Dictyostelium relative of UNC-104 transports liposomes containing acidic phospholipids, but whether this interaction is needed for the recognition and transport ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-04-0326

    authors: Klopfenstein DR,Vale RD

    更新日期:2004-08-01 00:00:00

  • The TAM-family receptor Mer mediates production of HGF through the RhoA-dependent pathway in response to apoptotic cells.

    abstract::The TAM receptor protein tyrosine kinases Tyro3, Axl, and Mer play important roles in macrophage function. We investigated the roles of the TAM receptors in mediating the induction of hepatocyte growth factor (HGF) during the interaction of macrophages with apoptotic cells. Mer-specific neutralizing antibody, small in...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E12-01-0029

    authors: Park HJ,Baen JY,Lee YJ,Choi YH,Kang JL

    更新日期:2012-08-01 00:00:00

  • Role of Akt and c-Jun N-terminal kinase 2 in apoptosis induced by interleukin-4 deprivation.

    abstract::We have shown previously that interleukin-4 (IL-4) protects TS1alphabeta cells from apoptosis, but very little is known about the mechanism by which IL-4 exerts this effect. We found that Akt activity, which is dependent on phosphatidylinositol 3 kinase, is reduced in IL-4-deprived TS1alphabeta cells. Overexpression o...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.9.11.3107

    authors: Cerezo A,Martínez-A C,Lanzarot D,Fischer S,Franke TF,Rebollo A

    更新日期:1998-11-01 00:00:00

  • Dissection of combinatorial control by the Met4 transcriptional complex.

    abstract::Met4 is the transcriptional activator of the sulfur metabolic network in Saccharomyces cerevisiae. Lacking DNA-binding ability, Met4 must interact with proteins called Met4 cofactors to target promoters for transcription. Two types of DNA-binding cofactors (Cbf1 and Met31/Met32) recruit Met4 to promoters and one cofac...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-05-0420

    authors: Lee TA,Jorgensen P,Bognar AL,Peyraud C,Thomas D,Tyers M

    更新日期:2010-02-01 00:00:00

  • A role for calmodulin in organelle membrane tubulation.

    abstract::Membrane tubules of uniform diameter (60-80 nm) and variable lengths have been seen to extend from the main bodies of the Golgi complex, trans Golgi network (TGN), and endosomes. In the case of endosomes, these tubules appear to mediate membrane and receptor recycling events. Brefeldin A (BFA) is a potent drug that co...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.6.7.871

    authors: de Figueiredo P,Brown WJ

    更新日期:1995-07-01 00:00:00

  • Multiple myosins are required to coordinate actin assembly with coat compression during compensatory endocytosis.

    abstract::Actin is involved in endocytosis in organisms ranging from yeast to mammals. In activated Xenopus eggs, exocytosing cortical granules (CGs) are surrounded by actin "coats," which compress the exocytosing compartments, resulting in compensatory endocytosis. Here, we examined the roles of two myosins in actin coat compr...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-11-0993

    authors: Yu HY,Bement WM

    更新日期:2007-10-01 00:00:00

  • Poleward transport of TPX2 in the mammalian mitotic spindle requires dynein, Eg5, and microtubule flux.

    abstract::TPX2 is a Ran-regulated spindle assembly factor that is required for kinetochore fiber formation and activation of the mitotic kinase Aurora A. TPX2 is enriched near spindle poles and is required near kinetochores, suggesting that it undergoes dynamic relocalization throughout mitosis. Using photoactivation, we measur...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-07-0601

    authors: Ma N,Tulu US,Ferenz NP,Fagerstrom C,Wilde A,Wadsworth P

    更新日期:2010-03-15 00:00:00

  • The catalytically inactive tyrosine phosphatase HD-PTP/PTPN23 is a novel regulator of SMN complex localization.

    abstract::The survival motor neuron (SMN) complex fulfils essential functions in the assembly of snRNPs, which are key components in the splicing of pre-mRNAs. Little is known about the regulation of SMN complex activity by posttranslational modification despite its complicated phosphorylation pattern. Several phosphatases had ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-06-1151

    authors: Husedzinovic A,Neumann B,Reymann J,Draeger-Meurer S,Chari A,Erfle H,Fischer U,Gruss OJ

    更新日期:2015-01-15 00:00:00

  • XGef mediates early CPEB phosphorylation during Xenopus oocyte meiotic maturation.

    abstract::Polyadenylation-induced translation is an important regulatory mechanism during metazoan development. During Xenopus oocyte meiotic progression, polyadenylation-induced translation is regulated by CPEB, which is activated by phosphorylation. XGef, a guanine exchange factor, is a CPEB-interacting protein involved in th...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-07-0585

    authors: Martínez SE,Yuan L,Lacza C,Ransom H,Mahon GM,Whitehead IP,Hake LE

    更新日期:2005-03-01 00:00:00

  • Direct binding of the ligand PSG17 to CD9 requires a CD9 site essential for sperm-egg fusion.

    abstract::The function currently attributed to tetraspanins is to organize molecular complexes in the plasma membrane by using multiple cis-interactions. Additionally, the tetraspanin CD9 may be a receptor that binds the soluble ligand PSG17, a member of the immunoglobulin superfamily (IgSF)/CEA subfamily. However, previous dat...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e03-04-0244

    authors: Ellerman DA,Ha C,Primakoff P,Myles DG,Dveksler GS

    更新日期:2003-12-01 00:00:00

  • C-terminus of the P4-ATPase ATP8A2 functions in protein folding and regulation of phospholipid flippase activity.

    abstract::ATP8A2 is a P4-ATPase that flips phosphatidylserine and phosphatidylethanolamine across cell membranes. This generates membrane phospholipid asymmetry, a property important in many cellular processes, including vesicle trafficking. ATP8A2 deficiency causes severe neurodegenerative diseases. We investigated the role of...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-06-0453

    authors: Chalat M,Moleschi K,Molday RS

    更新日期:2017-02-01 00:00:00

  • Novel genetic tools reveal Cdk5's major role in Golgi fragmentation in Alzheimer's disease.

    abstract::Golgi fragmentation is a common feature in multiple neurodegenerative diseases; however, the precise mechanism that causes fragmentation remains obscure. A potential link between Cdk5 and Golgi fragmentation in Alzheimer's disease (AD) was investigated in this study. Because Golgi is physiologically fragmented during ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-11-1106

    authors: Sun KH,de Pablo Y,Vincent F,Johnson EO,Chavers AK,Shah K

    更新日期:2008-07-01 00:00:00

  • Yeast exocytic v-SNAREs confer endocytosis.

    abstract::In yeast, homologues of the synaptobrevin/VAMP family of v-SNAREs (Snc1 and Snc2) confer the docking and fusion of secretory vesicles at the cell surface. As no v-SNARE has been shown to confer endocytosis, we examined whether yeast lacking the SNC genes, or possessing a temperature-sensitive allele of SNC1 (SNC1(ala4...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.10.3629

    authors: Gurunathan S,Chapman-Shimshoni D,Trajkovic S,Gerst JE

    更新日期:2000-10-01 00:00:00

  • Distribution and transport of cholesterol in Caenorhabditis elegans.

    abstract::Cholesterol transport is an essential process in all multicellular organisms. In this study we applied two recently developed approaches to investigate the distribution and molecular mechanisms of cholesterol transport in Caenorhabditis elegans. The distribution of cholesterol in living worms was studied by imaging it...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.6.1725

    authors: Matyash V,Geier C,Henske A,Mukherjee S,Hirsh D,Thiele C,Grant B,Maxfield FR,Kurzchalia TV

    更新日期:2001-06-01 00:00:00

  • Salmonella impairs RILP recruitment to Rab7 during maturation of invasion vacuoles.

    abstract::After invasion of epithelial cells, Salmonella enterica Typhimurium resides within membrane-bound vacuoles where it survives and replicates. Like endocytic vesicles, the Salmonella-containing vacuoles (SCVs) undergo a maturation process that involves sequential acquisition of Rab5 and Rab7 and displacement toward the ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-02-0092

    authors: Harrison RE,Brumell JH,Khandani A,Bucci C,Scott CC,Jiang X,Finlay BB,Grinstein S

    更新日期:2004-07-01 00:00:00

  • Activity of a ubiquitin ligase adaptor is regulated by disordered insertions in its arrestin domain.

    abstract::The protein composition of the plasma membrane is rapidly remodeled in response to changes in nutrient availability or cellular stress. This occurs, in part, through the selective ubiquitylation and endocytosis of plasma membrane proteins, which in the yeast Saccharomyces cerevisiae is mediated by the HECT E3 ubiquiti...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E19-08-0451

    authors: Baile MG,Guiney EL,Sanford EJ,MacGurn JA,Smolka MB,Emr SD

    更新日期:2019-12-01 00:00:00

  • Synaptic vesicles form by budding from tubular extensions of sorting endosomes in PC12 cells.

    abstract::The putative role of sorting early endosomes (EEs) in synaptic-like microvesicle (SLMV) formation in the neuroendocrine PC12 cell line was investigated by quantitative immunoelectron microscopy. By BSA-gold internalization kinetics, four distinct endosomal subcompartments were distinguished: primary endocytic vesicles...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.12.4163

    authors: de Wit H,Lichtenstein Y,Geuze HJ,Kelly RB,van der Sluijs P,Klumperman J

    更新日期:1999-12-01 00:00:00

  • Role of fission yeast Tup1-like repressors and Prr1 transcription factor in response to salt stress.

    abstract::In Schizosaccharomyces pombe, the Sty1 mitogen-activated protein kinase and the Atf1 transcription factor control transcriptional induction in response to elevated salt concentrations. Herein, we demonstrate that two repressors, Tup11 and Tup12, and the Prr1 transcription factor also function in the response to salt s...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.01-12-0568

    authors: Greenall A,Hadcroft AP,Malakasi P,Jones N,Morgan BA,Hoffman CS,Whitehall SK

    更新日期:2002-09-01 00:00:00

  • The BNIP-2 and Cdc42GAP homology (BCH) domain of p50RhoGAP/Cdc42GAP sequesters RhoA from inactivation by the adjacent GTPase-activating protein domain.

    abstract::The BNIP-2 and Cdc42GAP homology (BCH) domain is a novel regulator for Rho GTPases, but its impact on p50-Rho GTPase-activating protein (p50RhoGAP or Cdc42GAP) in cells remains elusive. Here we show that deletion of the BCH domain from p50RhoGAP enhanced its GAP activity and caused drastic cell rounding. Introducing c...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E09-05-0408

    authors: Zhou YT,Chew LL,Lin SC,Low BC

    更新日期:2010-09-15 00:00:00

  • Autoinhibition of Jak2 tyrosine kinase is dependent on specific regions in its pseudokinase domain.

    abstract::Jak tyrosine kinases have a unique domain structure containing a kinase domain (JH1) adjacent to a catalytically inactive pseudokinase domain (JH2). JH2 is crucial for inhibition of basal Jak activity, but the mechanism of this regulation has remained elusive. We show that JH2 negatively regulated Jak2 in bacterial ce...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-06-0342

    authors: Saharinen P,Vihinen M,Silvennoinen O

    更新日期:2003-04-01 00:00:00

  • Rer1p, a retrieval receptor for ER membrane proteins, recognizes transmembrane domains in multiple modes.

    abstract::The yeast Golgi membrane protein Rer1p is required for the retrieval of various endoplasmic reticulum (ER) membrane proteins such as Sec12p and Sec71p to the ER. We demonstrate here that the transmembrane domain (TMD) of Sec71p, a type-III membrane protein, contains an ER localization signal, which is required for phy...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-12-0777

    authors: Sato K,Sato M,Nakano A

    更新日期:2003-09-01 00:00:00

  • Mechanisms of plasma membrane targeting of formin mDia2 through its amino terminal domains.

    abstract::The formin mDia2 mediates the formation of lamellipodia and filopodia during cell locomotion. The subcellular localization of activated mDia2 depends on interactions with actin filaments and the plasma membrane. We investigated the poorly understood mechanism of plasma membrane targeting of mDia2 and found that the en...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E10-03-0256

    authors: Gorelik R,Yang C,Kameswaran V,Dominguez R,Svitkina T

    更新日期:2011-01-15 00:00:00

  • Fission yeast sts1+ gene encodes a protein similar to the chicken lamin B receptor and is implicated in pleiotropic drug-sensitivity, divalent cation-sensitivity, and osmoregulation.

    abstract::The Schizosaccharomyces pombe sts1+ gene, identified by supersensitive mutations to a protein kinase inhibitor, staurosporine, was isolated by complementation by the use of a fission yeast genomic library. Nucleotide sequencing shows that the sts1+ gene encodes a 453 amino acid putative membrane-associated protein tha...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.3.3.263

    authors: Shimanuki M,Goebl M,Yanagida M,Toda T

    更新日期:1992-03-01 00:00:00

  • Hse1, a component of the yeast Hrs-STAM ubiquitin-sorting complex, associates with ubiquitin peptidases and a ligase to control sorting efficiency into multivesicular bodies.

    abstract::Ubiquitinated integral membrane proteins are delivered to the interior of the lysosome/vacuole for degradation. This process relies on specific ubiquitination of potential cargo and recognition of that Ub-cargo by sorting receptors at multiple compartments. We show that the endosomal Hse1-Vps27 sorting receptor binds ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-06-0557

    authors: Ren J,Kee Y,Huibregtse JM,Piper RC

    更新日期:2007-01-01 00:00:00

  • Activated Cdc42-associated kinase 1 is a component of EGF receptor signaling complex and regulates EGF receptor degradation.

    abstract::Cdc42-associated tyrosine kinase 1 (ACK1) is a specific down-stream effector of Cdc42, a Rho family small G-protein. Previous studies have shown that ACK1 interacts with clathrin heavy chain and is involved in clathrin-coated vesicle endocytosis. Here we report that ACK1 interacted with epidermal growth factor recepto...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-02-0142

    authors: Shen F,Lin Q,Gu Y,Childress C,Yang W

    更新日期:2007-03-01 00:00:00

  • Organization of the yeast Golgi complex into at least four functionally distinct compartments.

    abstract::Pro-alpha-factor (pro-alphaf) is posttranslationally modified in the yeast Golgi complex by the addition of alpha1,6-, alpha1,2-, and alpha1,3-linked mannose to N-linked oligosaccharides and by a Kex2p-initiated proteolytic processing event. Previous work has indicated that the alpha1,6- and alpha1,3-mannosylation and...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.1.171

    authors: Brigance WT,Barlowe C,Graham TR

    更新日期:2000-01-01 00:00:00