Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex.


:An important signaling pathway to the actin cytoskeleton links the Rho family GTPase Cdc42 to the actin-nucleating Arp2/3 complex through N-WASP. Nevertheless, these previously identified components are not sufficient to mediate Cdc42-induced actin polymerization in a physiological context. In this paper, we describe the biochemical purification of Toca-1 (transducer of Cdc42-dependent actin assembly) as an essential component of the Cdc42 pathway. Toca-1 binds both N-WASP and Cdc42 and is a member of the evolutionarily conserved PCH protein family. Toca-1 promotes actin nucleation by activating the N-WASP-WIP/CR16 complex, the predominant form of N-WASP in cells. Thus, the cooperative actions of two distinct Cdc42 effectors, the N-WASP-WIP complex and Toca-1, are required for Cdc42-induced actin assembly. These findings represent a significantly revised view of Cdc42-signaling and shed light on the pathogenesis of Wiskott-Aldrich syndrome.






Ho HY,Rohatgi R,Lebensohn AM,Le Ma,Li J,Gygi SP,Kirschner MW




Has Abstract


2004-07-23 00:00:00
















  • Mechanism of replication-coupled DNA interstrand crosslink repair.

    abstract::DNA interstrand crosslinks (ICLs) are toxic DNA lesions whose repair occurs in the S phase of metazoans via an unknown mechanism. Here, we describe a cell-free system based on Xenopus egg extracts that supports ICL repair. During DNA replication of a plasmid containing a site-specific ICL, two replication forks conver...


    pub_type: 杂志文章


    authors: Räschle M,Knipscheer P,Enoiu M,Angelov T,Sun J,Griffith JD,Ellenberger TE,Schärer OD,Walter JC

    更新日期:2008-09-19 00:00:00

  • Molecular architecture of annelid nerve cord supports common origin of nervous system centralization in bilateria.

    abstract::To elucidate the evolutionary origin of nervous system centralization, we investigated the molecular architecture of the trunk nervous system in the annelid Platynereis dumerilii. Annelids belong to Bilateria, an evolutionary lineage of bilateral animals that also includes vertebrates and insects. Comparing nervous sy...


    pub_type: 杂志文章


    authors: Denes AS,Jékely G,Steinmetz PR,Raible F,Snyman H,Prud'homme B,Ferrier DE,Balavoine G,Arendt D

    更新日期:2007-04-20 00:00:00

  • Promoter-specific transcription inhibition in Staphylococcus aureus by a phage protein.

    abstract::Phage G1 gp67 is a 23 kDa protein that binds to the Staphylococcus aureus (Sau) RNA polymerase (RNAP) σ(A) subunit and blocks cell growth by inhibiting transcription. We show that gp67 has little to no effect on transcription from most promoters but is a potent inhibitor of ribosomal RNA transcription. A 2.0-Å-resolut...


    pub_type: 杂志文章


    authors: Osmundson J,Montero-Diez C,Westblade LF,Hochschild A,Darst SA

    更新日期:2012-11-21 00:00:00

  • Both layers of the COPII coat come into view.

    abstract::Anterograde transport in the early secretory pathway is mediated by COPII-coated vesicles. Stagg et al. (2008) have now visualized the double-layered COPII coat using electron cryomicroscopy, providing insight into how coats are assembled to accommodate cargo of different sizes. ...


    pub_type: 评论,杂志文章


    authors: Hughson FM

    更新日期:2008-08-08 00:00:00

  • Sterol-regulated release of SREBP-2 from cell membranes requires two sequential cleavages, one within a transmembrane segment.

    abstract::Sterol regulatory element binding proteins (SREBPs) are transcription factors attached to the endoplasmic reticulum. The NH2-segment, which activates transcription, is connected to membranes by a hairpin anchor formed by two transmembrane sequences and a short lumenal loop. Using H-Ras-SREBP-2 fusion proteins, we show...


    pub_type: 杂志文章


    authors: Sakai J,Duncan EA,Rawson RB,Hua X,Brown MS,Goldstein JL

    更新日期:1996-06-28 00:00:00

  • Inhibition of receptor-mediated release of arachidonic acid by pertussis toxin.

    abstract::Treatment of guinea pig neutrophils with pertussis toxin (islet-activating protein; IAP) results in inhibition of N-formyl peptide receptor-mediated release of arachidonic acid and granular enzymes. Inhibition by the toxin is specific, in that responses to the calcium ionophore A23187 are not affected. The action of t...


    pub_type: 杂志文章


    authors: Bokoch GM,Gilman AG

    更新日期:1984-12-01 00:00:00

  • Controlling Visually Guided Behavior by Holographic Recalling of Cortical Ensembles.

    abstract::Neurons in cortical circuits are often coactivated as ensembles, yet it is unclear whether ensembles play a functional role in behavior. Some ensemble neurons have pattern completion properties, triggering the entire ensemble when activated. Using two-photon holographic optogenetics in mouse primary visual cortex, we ...


    pub_type: 杂志文章


    authors: Carrillo-Reid L,Han S,Yang W,Akrouh A,Yuste R

    更新日期:2019-07-11 00:00:00

  • Distinct Ventral Pallidal Neural Populations Mediate Separate Symptoms of Depression.

    abstract::Major depressive disorder (MDD) patients display a common but often variable set of symptoms making successful, sustained treatment difficult to achieve. Separate depressive symptoms may be encoded by differential changes in distinct circuits in the brain, yet how discrete circuits underlie behavioral subsets of depre...


    pub_type: 杂志文章


    authors: Knowland D,Lilascharoen V,Pacia CP,Shin S,Wang EH,Lim BK

    更新日期:2017-07-13 00:00:00

  • TGF-beta signaling specifies axons during brain development.

    abstract::In the mammalian brain, the specification of a single axon and multiple dendrites occurs early in the differentiation of most neuron types. Numerous intracellular signaling events for axon specification have been described in detail. However, the identity of the extracellular factor(s) that initiate neuronal polarity ...


    pub_type: 杂志文章


    authors: Yi JJ,Barnes AP,Hand R,Polleux F,Ehlers MD

    更新日期:2010-07-09 00:00:00

  • A large inverted duplication allows homologous recombination between chromosomes heterozygous for the proximal t complex inversion.

    abstract::We have examined the molecular organization of a region of mouse chromosome 17 that allows homologous recombination between wild-type and t haplotype chromosomes across a large inversion. We have used a combination of genetic mapping of restriction fragment length polymorphisms, molecular characterization of cloned re...


    pub_type: 杂志文章


    authors: Herrmann BG,Barlow DP,Lehrach H

    更新日期:1987-03-13 00:00:00

  • G1-specific cyclins of S. cerevisiae: cell cycle periodicity, regulation by mating pheromone, and association with the p34CDC28 protein kinase.

    abstract::The S. cerevisiae CLN genes encode cyclin homologs essential for progression from G1 to S phase. The CLN2 gene encodes a 62 kd polypeptide that accumulates periodically, peaking during G1 and decreasing rapidly thereafter, and is rapidly lost following exposure of cells to mating pheromone. Cln2 abundance can be expla...


    pub_type: 杂志文章


    authors: Wittenberg C,Sugimoto K,Reed SI

    更新日期:1990-07-27 00:00:00

  • MICU1 is an essential gatekeeper for MCU-mediated mitochondrial Ca(2+) uptake that regulates cell survival.

    abstract::Mitochondrial Ca(2+) (Ca(2+)(m)) uptake is mediated by an inner membrane Ca(2+) channel called the uniporter. Ca(2+) uptake is driven by the considerable voltage present across the inner membrane (ΔΨ(m)) generated by proton pumping by the respiratory chain. Mitochondrial matrix Ca(2+) concentration is maintained five ...


    pub_type: 杂志文章


    authors: Mallilankaraman K,Doonan P,Cárdenas C,Chandramoorthy HC,Müller M,Miller R,Hoffman NE,Gandhirajan RK,Molgó J,Birnbaum MJ,Rothberg BS,Mak DO,Foskett JK,Madesh M

    更新日期:2012-10-26 00:00:00

  • Organization of the ribosomal RNA genes of Dictyostelium discoideum: mapping of the nontranscribed spacer regions.

    abstract::Most of the Dictyostelium ribosomal nontranscribed spacer DNA has been mapped using Eco R1, Hind III, and Sal I restriction digests and recombinant plasmids containing parts of the rDNA (ribosomal DNA). The repeat units are at least 42 kb (1 kilobase = 1000 base pairs = 1 kb) long; of this, 8 kb codes for the 36S rRNA...


    pub_type: 杂志文章


    authors: Cockburn AF,Newkirk MJ,Firtel RA

    更新日期:1976-12-01 00:00:00

  • Treatment of obesity with celastrol.

    abstract::Despite all modern advances in medicine, an effective drug treatment of obesity has not been found yet. Discovery of leptin two decades ago created hopes for treatment of obesity. However, development of leptin resistance has been a big obstacle, mitigating a leptin-centric treatment of obesity. Here, by using in sili...


    pub_type: 杂志文章


    authors: Liu J,Lee J,Salazar Hernandez MA,Mazitschek R,Ozcan U

    更新日期:2015-05-21 00:00:00

  • RNA Sensing by Gut Piezo1 Is Essential for Systemic Serotonin Synthesis.

    abstract::Gastrointestinal enterochromaffin cells regulate bone and gut homeostasis via serotonin (5-hydroxytryptamine [5-HT]) production. A recent report suggested that gut microbes regulate 5-HT levels; however, the precise underlying molecular mechanisms are unexplored. Here, we reveal that the cation channel Piezo1 in the g...


    pub_type: 杂志文章


    authors: Sugisawa E,Takayama Y,Takemura N,Kondo T,Hatakeyama S,Kumagai Y,Sunagawa M,Tominaga M,Maruyama K

    更新日期:2020-08-06 00:00:00

  • Function of retinoic acid receptor gamma in the mouse.

    abstract::Null mutant mice for retinoic acid receptor gamma 2 (RAR gamma 2) or all RAR gamma isoforms were generated. RAR gamma 2 mutants appeared normal, whereas RAR gamma mutants exhibited growth deficiency, early lethality, and male sterility due to squamous metaplasia of the seminal vesicles and prostate. These defects were...


    pub_type: 杂志文章


    authors: Lohnes D,Kastner P,Dierich A,Mark M,LeMeur M,Chambon P

    更新日期:1993-05-21 00:00:00

  • Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

    abstract::Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTE...


    pub_type: 杂志文章


    authors: Ciriello G,Gatza ML,Beck AH,Wilkerson MD,Rhie SK,Pastore A,Zhang H,McLellan M,Yau C,Kandoth C,Bowlby R,Shen H,Hayat S,Fieldhouse R,Lester SC,Tse GM,Factor RE,Collins LC,Allison KH,Chen YY,Jensen K,Johnson NB,O

    更新日期:2015-10-08 00:00:00

  • Corticoamygdala Transfer of Socially Derived Information Gates Observational Learning.

    abstract::Observational learning is a powerful survival tool allowing individuals to learn about threat-predictive stimuli without directly experiencing the pairing of the predictive cue and punishment. This ability has been linked to the anterior cingulate cortex (ACC) and the basolateral amygdala (BLA). To investigate how inf...


    pub_type: 杂志文章


    authors: Allsop SA,Wichmann R,Mills F,Burgos-Robles A,Chang CJ,Felix-Ortiz AC,Vienne A,Beyeler A,Izadmehr EM,Glober G,Cum MI,Stergiadou J,Anandalingam KK,Farris K,Namburi P,Leppla CA,Weddington JC,Nieh EH,Smith AC,Ba D,Bro

    更新日期:2018-05-31 00:00:00

  • Identification of regulators of polyploidization presents therapeutic targets for treatment of AMKL.

    abstract::The mechanism by which cells decide to skip mitosis to become polyploid is largely undefined. Here we used a high-content image-based screen to identify small-molecule probes that induce polyploidization of megakaryocytic leukemia cells and serve as perturbagens to help understand this process. Our study implicates fi...


    pub_type: 杂志文章


    authors: Wen Q,Goldenson B,Silver SJ,Schenone M,Dancik V,Huang Z,Wang LZ,Lewis TA,An WF,Li X,Bray MA,Thiollier C,Diebold L,Gilles L,Vokes MS,Moore CB,Bliss-Moreau M,Verplank L,Tolliday NJ,Mishra R,Vemula S,Shi J,Wei L

    更新日期:2012-08-03 00:00:00

  • Isolation and characterization of the nuclear matrix in Friend erythroleukemia cells: chromatin and hnRNA interactions with the nuclear matrix.

    abstract::Nuclear matrices from undifferentiated and differentiated Friend erythroleukemia cells have been obtained by a method which removes DNA in a physiological buffer. These matrices preserved the characteristic topographical distribution of condensed and diffuse "chromatin" regions, as do nuclei in situ or isolated nuclei...


    pub_type: 杂志文章


    authors: Long BH,Huang CY,Pogo AO

    更新日期:1979-12-01 00:00:00

  • The cryb mutation identifies cryptochrome as a circadian photoreceptor in Drosophila.

    abstract::A new rhythm mutation was isolated based on its elimination of per-controlled luciferase cycling. Levels of period or timeless clock gene products in the mutant are flat in daily light-dark cycles or constant darkness (although PER and TIM oscillate normally in temperature cycles). Consistent with the fact that light ...


    pub_type: 杂志文章


    authors: Stanewsky R,Kaneko M,Emery P,Beretta B,Wager-Smith K,Kay SA,Rosbash M,Hall JC

    更新日期:1998-11-25 00:00:00

  • A secondary attachment site for bacteriophage lambda in trpC of E. coli.

    abstract::We have determined the nucleotide sequence of a secondary lambda attachment site in trpC. Direct sequence analysis of lambdatrp transducing phage DNA fragments carrying the two prophage attachment sites reveals a 6 nucleotide homology in the crossover region which is a subset of the 15 nucleotide core sequence in the ...


    pub_type: 杂志文章


    authors: Christie GE,Platt T

    更新日期:1979-02-01 00:00:00

  • Mice expressing activated CaMKII lack low frequency LTP and do not form stable place cells in the CA1 region of the hippocampus.

    abstract::To relate different forms of synaptic plasticity to the formation and maintenance of place cells in the hippocampus, we have recorded place cells in freely behaving, transgenic mice that express a mutated Ca2+-independent form of CaM Kinase II. These mice have normal long-term potentiation (LTP) at 100 Hz, but they la...


    pub_type: 杂志文章


    authors: Rotenberg A,Mayford M,Hawkins RD,Kandel ER,Muller RU

    更新日期:1996-12-27 00:00:00

  • Retinoic acid signaling is essential for embryonic hematopoietic stem cell development.

    abstract::Hematopoietic stem cells (HSCs) develop from a specialized subpopulation of endothelial cells known as hemogenic endothelium (HE). Although the HE origin of HSCs is now well established in different species, the signaling pathways that control this transition remain poorly understood. Here, we show that activation of ...


    pub_type: 杂志文章


    authors: Chanda B,Ditadi A,Iscove NN,Keller G

    更新日期:2013-09-26 00:00:00

  • Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling.

    abstract::Synapse formation requires changes in cell morphology and the upregulation and localization of synaptic proteins. In the cerebellum, mossy fibers undergo extensive remodeling as they contact several granule cells and form complex, multisynaptic glomerular rosettes. Here we show that granule cells secrete factors that ...


    pub_type: 杂志文章


    authors: Hall AC,Lucas FR,Salinas PC

    更新日期:2000-03-03 00:00:00

  • Mutations in the gene for EF-G reduce the requirement for 4.5S RNA in the growth of E. coli.

    abstract::A general strategy is described for the isolation of suppressors of essential genes whose functions are unknown. This strategy was used to analyze the role of 4.5S RNA, an essential RNA of E. coli. In this strategy, the structural gene for 4.5S RNA is fused to the Ptac promoter in such a way that the strain becomes de...


    pub_type: 杂志文章


    authors: Brown S

    更新日期:1987-06-19 00:00:00

  • Regulatory Expansion in Mammals of Multivalent hnRNP Assemblies that Globally Control Alternative Splicing.

    abstract::Alternative splicing (AS) patterns have diverged rapidly during vertebrate evolution, yet the functions of most species- and lineage-specific splicing events are not known. We observe that mammalian-specific AS events are enriched in transcript sequences encoding intrinsically disordered regions (IDRs) of proteins, in...


    pub_type: 杂志文章


    authors: Gueroussov S,Weatheritt RJ,O'Hanlon D,Lin ZY,Narula A,Gingras AC,Blencowe BJ

    更新日期:2017-07-13 00:00:00

  • Molecular genetics of the achaete-scute gene complex of D. melanogaster.

    abstract::The achaete-scute gene complex (AS-C), involved in differentiation of the sensory chaetes of D. melanogaster, and the yellow locus have been cloned. The yellow locus is the most distal and is followed, proximally, by the achaete and the scute loci. In the scute locus (75 kb), three transcription units separated by lon...


    pub_type: 杂志文章


    authors: Campuzano S,Carramolino L,Cabrera CV,Ruíz-Gómez M,Villares R,Boronat A,Modolell J

    更新日期:1985-02-01 00:00:00

  • Increased expression of neurofilament subunit NF-L produces morphological alterations that resemble the pathology of human motor neuron disease.

    abstract::Excessive accumulation of neurofilaments in the cell bodies and proximal axons of motor neurons is a major pathological hallmark during the early stages of many human motor neuron diseases. To test directly the consequence of overexpression of the major neurofilament subunit NF-L, we produced transgenic mice that accu...


    pub_type: 杂志文章


    authors: Xu Z,Cork LC,Griffin JW,Cleveland DW

    更新日期:1993-04-09 00:00:00

  • Remarkable conservation of structure among intermediate filament genes.

    abstract::Using a cloned cDNA complementary to a portion of the mRNA for the 50 kd human epidermal keratin, we have screened a human genomic library and have isolated and sequenced the gene encoding this keratin. A comparison of the keratin gene with the very distantly related vimentin gene has enabled us to explore the relatio...


    pub_type: 杂志文章


    authors: Marchuk D,McCrohon S,Fuchs E

    更新日期:1984-12-01 00:00:00