Nature Cell Biology contents: April 2012 Volume 14 Number 4, pp 331 - 437

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See it online only at Duolink-vs-CoIP.com Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Combine INCUBATOR and READER: 2-in-1 Tecan's NEW CO2/O2 Gas Control Module for Infinite 200 PRO!  • Consistent physiological conditions  • Simultaneous CO2 and O2  • No transport of cell cultures from incubator to reader  • Complete data sets overnight Learn more   Advertisement Nature Outlook: Lenses on Biology In this special edition of Nature Outlook, five top scientists explain how research in their specialties - cancer, climate change, stem cells, oceanography and synthetic biology - has changed our lives. Access the Outlook free online for six months. Produced in partnership with Nature Education.   Comment Top Stem cell biology: Towards the reality of cell therapeutics p331 Alan Trounson and Natalie D. DeWitt doi:10.1038/ncb2469 Although the road to cell therapeutics is rife with uncertainties — scientific, clinical and economic — its success could transform medicine. Five years into its mission, the California Institute of Regenerative Medicine is laying a foundation for this new form of medical treatment. Full Text | PDF Turning Points Top Into the deep: Refocusing on 3D p332 Joan S. Brugge doi:10.1038/ncb2470 Full Text | PDF News and Views Top A numbers game underpins cytoplasmic mRNA transport pp333 - 335 Michael Doyle and Michael A. Kiebler doi:10.1038/ncb2475 Microtubule-based mRNA transport participates in the establishment of cell asymmetries. An in vitro reconstitution assay demonstrates that localization signals present in an mRNA influence motor copy number on single RNA molecule cargoes, ultimately leading to highly polarized distributions of transcripts. Full Text | PDF See also: Letter by Amrute-Nayak & Bullock Robustness in crossover regulation during meiosis pp335 - 337 Chitra V. Kotwaliwale doi:10.1038/ncb2474 Meiotic recombination produces physical linkages between homologous chromosomes that enable their segregation to opposite poles during meiosis I. In the absence of recombination, chromosomes mis-segregate, resulting in aneuploidy associated with severe birth defects. A recent study provides exciting insights into how recombination is fine-tuned to enforce a robust meiotic program. Full Text | PDF See also: Letter by Cole et al. Twists and turns of invasion pp337 - 339 Geoffrey Childs and Jeffrey E. Segall doi:10.1038/ncb2477 The transcription factor Twist1 is overexpressed in tumours and can induce the epithelial-mesenchymal transition, resulting in increased invasiveness. Twist1 is now shown to regulate cancer cell migration and invasion in three-dimensional environments by activating the RAC1 GTPase through suppression of a let-7 microRNA family member. Full Text | PDF See also: Article by Yang et al. Signalling the end of the line pp339 - 341 John van Tuyn and Peter D. Adams doi:10.1038/ncb2476 Cellular senescence is a stable proliferation arrest induced by triggers such as short telomeres, activated oncogenes and genotoxic stress. Two studies show that cellular senescence induced by genotoxic stress depends on chronic DNA-damage signalling from irreparable damage to telomeres. Hence, dysfunctional or damaged telomeres are the initiators of multiple modes of senescence. Full Text | PDF See also: Article by Fumagalli et al. Cell Biology JOBS of the week Postdoctoral fellow Lund University, Cell and Experimental Pathology Research Associate / Senior Research Associate in Stem Cell Research Advanced Cell Technology (ACT) Lab Technician Boston University - Department of Medicine - Richard A. Cohen Vascular Biology Unit PostDoc Position; Lipid Sensing, Signaling and Apoptosis Molecular Cell Biology Division, University of Osnabrueck Postdoc International Institute of Molecular and Cell Biology in Warsaw More Science jobs from Cell Biology EVENT 3rd International Conference on Stem Cell Engineering 29.04.-02.05.12 Seattle, US More science events from Research Highlights Top Sensing microtubule dynamics | MicroRNAs in angiogenesis | Sec-rets of COPII coat formation | Escaping normal tissue constraints in cancer Advertisement Small Reactor - Great Results With CELLSTAR® CELLreactor™ 50 ml Polypropylene Filter Top Tube • Innovative: Small bioreactor for suspension culture of • cells and other microorganisms • Safe: USP VI-certified PTFE-coated capillary • membrane with 0,2 µm pore size • Fast: Facilitates high number of parallel experiments • Hassle-free: Cultivation and harvest in one tube • Easy: Mixing by standard shaking equipment More: www.gbo.com/bioscience   Articles Top A 14-3-3γ dimer-based scaffold bridges CtBP1-S/BARS to PI(4)KIIIβ to regulate post-Golgi carrier formation pp343 - 354 Carmen Valente, Gabriele Turacchio, Stefania Mariggiò, Alessandro Pagliuso, Renato Gaibisso, Giuseppe Di Tullio, Michele Santoro, Fabio Formiggini, Stefania Spanò, Daniele Piccini, Roman S. Polishchuk, Antonino Colanzi, Alberto Luini and Daniela Corda doi:10.1038/ncb2445 Formation and fission of large membrane-bound carriers at the Golgi requires coordinated action by a myriad of proteins, including PI(4)KIIIβ and CtBP1-S/BARS. Corda and colleagues reveal that the scaffold protein 14-3-3γ bridges BARS to PI(4)KIIIβ, thus mechanistically linking carrier budding and tubulation with tubule fission. Abstract | Full Text | PDF Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation pp355 - 365 Marzia Fumagalli, Francesca Rossiello, Michela Clerici, Sara Barozzi, Davide Cittaro, Jessica M. Kaplunov, Gabriele Bucci, Miryana Dobreva, Valentina Matti, Christian M. Beausejour, Utz Herbig, Maria Pia Longhese and Fabrizio d'Adda di Fagagna doi:10.1038/ncb2466 D'Adda di Fagagna and colleagues observe that, after genotoxic treatment of cells and mice, unrepaired DNA-damage foci and DNA-damage signalling persist at telomeres. They show that introducing the telomeric protein TRF2 near a double-strand break elsewhere on the chromosomes prevents repair. Unrepaired foci are also observed at telomeres of ageing animals, suggesting a role for TRF2 in senescence establishment. Abstract | Full Text | PDF See also: News and Views by van Tuyn & Adams RAC1 activation mediates Twist1-induced cancer cell migration pp366 - 374 Wen-Hao Yang, Hsin-Yi Lan, Chi-Hung Huang, Shyh-Kuan Tai, Cheng-Hwai Tzeng, Shou-Yen Kao, Kou-Juey Wu, Mien-Chie Hung and Muh-Hwa Yang doi:10.1038/ncb2455 Yang and colleagues delineate a pathway that controls cell migration in 3D environments following Twist1-mediated epithelial-to-mesenchymal transition. They show that Twist1 represses the let-7i microRNA, leading to upregulation of the RAC1-activating factors NEDD9 and DOCK3, and inducing mesenchymal-mode motility and tumour invasion in vivo. Abstract | Full Text | PDF See also: News and Views by Childs & Segall Fbxw7α- and GSK3-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma pp375 - 385 Luca Busino, Scott E. Millman, Luigi Scotto, Christos A. Kyratsous, Venkatesha Basrur, Owen O'Connor, Alexander Hoffmann, Kojo S. Elenitoba-Johnson and Michele Pagano doi:10.1038/ncb2463 The SCF ubiquitin ligase subunit Fbxw7 is a tumour suppressor that is mutated in many cancers. Pagano and colleagues now show that in multiple myeloma, Fbxw7α instead functions as a pro-survival factor by activating the NF-κB pathway through the ubiquitin-mediated degradation of p100, an NF-κB pathway inhibitor. Abstract | Full Text | PDF Letters Top Whacked and Rab35 polarize dynein-motor-complex-dependent seamless tube growth pp386 - 393 Jodi Schottenfeld-Roames and Amin S. Ghabrial doi:10.1038/ncb2454 Seamless tubes are found in Drosophila tracheal terminal cells, but it is still unclear how they grow. Ghabrial and colleagues find that the small GTPase Rab35, and its apically localized GAP, Whacked, direct tube shape and growth. They also highlight a role for dynein in this process. First paragraph | Full Text | PDF Direct sensing of systemic and nutritional signals by haematopoietic progenitors in Drosophila  pp394 - 400 Jiwon Shim, Tina Mukherjee and Utpal Banerjee doi:10.1038/ncb2453 Haematopoietic progenitor activity in the Drosophila lymph gland can respond to stress. Banerjee and colleagues show that systemic insulin and nutritional signals maintain these progenitors by modulating Wingless-dependent pathways. First paragraph | Full Text | PDF Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling pp401 - 408 Vivian W. Y. Wong, Daniel E. Stange, Mahalia E. Page, Simon Buczacki, Agnieszka Wabik, Satoshi Itami, Marc van de Wetering, Richard Poulsom, Nicholas A. Wright, Matthew W. B. Trotter, Fiona M. Watt, Doug J. Winton, Hans Clevers and Kim B. Jensen doi:10.1038/ncb2464 Lrig1, a transmembrane glycoprotein, has previously been shown to inhibit ErbB signalling. Jensen and colleagues show that Lrig1 controls the size of the intestinal stem-cell niche by modulating the amplitude of ErbB signalling. Thus, ErbB activation acts in concert with Wnt, Notch and Bmpr inhibition, to modulate stem-cell proliferation in the crypt. First paragraph | Full Text | PDF CDK5 and MEKK1 mediate pro-apoptotic signalling following endoplasmic reticulum stress in an autosomal dominant retinitis pigmentosa model pp409 - 415 Min-Ji Kang, Jaehoon Chung and Hyung Don Ryoo doi:10.1038/ncb2447 ER stress activates the unfolded protein response (UPR), which can ultimately result in apoptosis. Using a Drosophila model of ER stress, Ryoo and colleagues find that apoptosis is induced independently of the known UPR branches. They show that ER stress induces CDK5-mediated phosphorylation of MEKK1, which activates JNK and induces apoptosis. First paragraph | Full Text | PDF Single-molecule assays reveal that RNA localization signals regulate dynein-dynactin copy number on individual transcript cargoes pp416 - 423 Mamta Amrute-Nayak and Simon L. Bullock doi:10.1038/ncb2446 Bullock and colleagues have reconstituted in vitro the microtubule-driven transport of RNAs to specific localizations in Drosophila melanogaster embryos. They show that a set of localized messenger nucleoproteins (mRNPs) exhibits a strong bias in motility towards microtubule minus ends, correlating with an increase in the binding of dynein components (when compared with non-localizing bidirectionally moving mRNPs). They also find that a single mRNA transcript can be found within motile mRNPs, both in vitro and in vivo. First paragraph | Full Text | PDF See also: News and Views by Doyle & Kiebler Homeostatic control of recombination is implemented progressively in mouse meiosis pp424 - 430 Francesca Cole, Liisa Kauppi, Julian Lange, Ignasi Roig, Raymond Wang, Scott Keeney and Maria Jasin doi:10.1038/ncb2451 Meiotic recombination involves the generation of double-strand breaks, that needs to be carefully controlled to avoid fetal aneuploidy. In worms and yeast, crossover numbers are constant regardless of the amount of double-strand breaks. Jasin and colleagues now show that such crossover homeostasis mechanisms exist at two stages in mammalian meiosis. First paragraph | Full Text | PDF See also: News and Views by Kotwaliwale A size-exclusion permeability barrier and nucleoporins characterize a ciliary pore complex that regulates transport into cilia pp431 - 437 Hooi Lynn Kee, John F. Dishinger, T. Lynne Blasius, Chia-Jen Liu, Ben Margolis and Kristen J. Verhey doi:10.1038/ncb2450 Entry into the cilium is restricted by a network of proteins at its base. Verhey and colleagues now show that nucleoporins, which localize to the nuclear envelope and regulate nuclear-cytoplasmic traffic, are also present at the cilium base, where they form a size-dependent exclusion barrier. First paragraph | Full Text | PDF Top Advertisement Take a look at this article that recently published in Oncogenesis! 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