Nature Cell Biology contents: September 2012 Volume 14 Number 9, pp 891 - 976

Advertisement Get accurate fluorescence measurements with Hamamatsu detectors for FCS, FLIM, and confocal and two-photon microscopy. For FCS and FLIM, we offer hybrid photodetectors (HPD) with high sensitivity, high speed, and very low afterpulsing. For confocal and two-photon microscopy, we offer easy-to-use GaAsP/GaAs PMT modules featuring high sensitivity and large active areas. Several PMT module configurations are available. TABLE OF CONTENTS September 2012 Volume 14, Issue 9 Editorial Review News and Views Research Highlights Articles Letters Resource Advertisement Powerfully Simple - Operetta High Content Imaging System Don't let your high content analysis be hindered by confusing technology and complicated software. With the Operetta® High Content Imaging System, you get the power and simplicity you need to quickly and easily turn images into unbiased quantitative data and advance your research. Watch the video and see for yourself! Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement One-STrEP-tag the high affinity Strep-tag II   One-STrEP-tag combines high affinity with high specifity, therefore allowing isolation of highly pure and functional proteins even from batch. Mild elution conditions preserve protein complexes and protein interactions... Click here for application examples    Editorial Top Science and politics: Picking a winner   p891 doi:10.1038/ncb2575 The candidates for the office of President of the United States have declared opinions and traded jabs on a wide range of topics that affect the country's global reach. However, key scientific areas in which the US must show leadership, such as climate change, science education and scientific research funding, have yet to take centre stage. Review Top Lineage conversion methodologies meet the reprogramming toolbox   pp892 - 899 Ignacio Sancho-Martinez, Sung Hee Baek and Juan Carlos Izpisua Belmonte doi:10.1038/ncb2567 Lineage conversion has recently attracted increasing attention as a potential alternative to the directed differentiation of pluripotent cells to obtain cells of a given lineage. Different means allowing for cell identity switch have been reported. Lineage conversion relied initially on the discovery of specific transcription factors generally enriched and characteristic of the target cell, and their forced expression in cells of a different fate. This approach has been successful in various cases, from cells of the hematopoietic systems to neurons and cardiomyocytes. Furthermore, recent reports have suggested the possibility of establishing a general lineage conversion approach bypassing pluripotency. This requires a first phase of epigenetic erasure achieved by short overexpression of the factors used to reprogram cells to a pluripotent state (such as a combination of Sox2, Klf4, c-Myc and Oct4), followed by exposure to specific developmental cues. Here we present these different direct conversion methodologies and discuss their potential as alternatives to using induced pluripotent stem cells and differentiation protocols to generate cell populations of a given fate. News and Views Top Visualizing global effects of the DNA damage response   pp900 - 901 Peter H. Thorpe and Rodney Rothstein doi:10.1038/ncb2571 In a large-scale analysis, the effects of DNA damage on the levels and localization of almost every protein in an organism have now been tracked in living cells. It is shown that that although many proteins change their position or concentration, they rarely do both. See also: Resource by Tkach et al. A cellular sense of touch   pp902 - 903 Li He and Denise Montell doi:10.1038/ncb2572 How cells sense and respond to physical forces is an area of intense investigation, which poses significant challenges for in vitro experiments and even greater obstacles for in vivo studies. Analyses of integrin complex dynamics in Drosophila melanogaster now provide evidence that altering mechanical force modulates the stability of integrin adhesion in vivo. See also: Letter by Pines et al. Regulating intraflagellar transport   pp904 - 906 Lotte B. Pedersen and Søren T. Christensen doi:10.1038/ncb2569 Kinesin-2 motors mediate anterograde intraflagellar transport (IFT) of IFT particles from the ciliary base to its tip, where particles are remodelled before retrograde transport by dynein 2 motors. Bardet-Biedl syndrome (BBS) and IFT-A proteins are now implicated in regulation of IFT assembly at the ciliary base and tip. See also: Letter by Wei et al. Bending membranes   pp906 - 908 Tom Kirchhausen doi:10.1038/ncb2570 It is widely assumed that peripheral membrane proteins induce intracellular membrane curvature by the asymmetric insertion of a protein segment into the lipid bilayer, or by imposing shape by adhesion of a curved protein domain to the membrane surface. Two papers now provide convincing evidence challenging these views. The first shows that specific assembly of a clathrin protein scaffold, coupled to the membrane, seems to be the most prevalent mechanism for bending a lipid bilayer in a cell. The second reports that membrane crowding, driven by protein-protein interactions, can also drive membrane bending, even in the absence of any protein insertion into the bilayer. See also: Letter by Stachowiak et al. Cell Biology JOBS of the week Research Associate in Molecular Cell Biology Cambridge University, Metabolic Research Laboratories cell migration Institut Curie UMR 144 Professorship For Cell Biology And Genetics University of Salzburg Postdoc in Stem Cell Research in NIEHS / NIH (RTP, NC) National Institute of Environmental Health Sciences (NIEHS) Tenure-track assistant professor of molecular cell biology Department Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University More Science jobs from Cell Biology EVENT Biosimilars and Biobetters 24.-25.09.12 London, Uk More science events from Research Highlights Top p70S6K and AMPK converge for weight control | Keeping warm with beige adipocytes | Atg9 vesicles make up autophagosomes | Cancer stem cells revealed in vivo Advertisement Solution savings: Best-in-class bead-based immunoassays  With a combined value package you can save 10% on the BD Accuri™ C6 personal flow cytometer, 40% on BD™ CBA reagents for 2 full years, plus $6,500 worth of free software and cytometer options. There's never been a better time to buy the best-in-class solution for bead-based immunoassays. bdbiosciences.com/go/c6beads   Articles Top CDKL5 ensures excitatory synapse stability by reinforcing NGL-1–PSD95 interaction in the postsynaptic compartment and is impaired in patient iPSC-derived neurons   pp911 - 923 Sara Ricciardi, Federica Ungaro, Melanie Hambrock, Nils Rademacher, Gilda Stefanelli, Dario Brambilla, Alessandro Sessa, Cinzia Magagnotti, Angela Bachi, Elisa Giarda, Chiara Verpelli, Charlotte Kilstrup-Nielsen, Carlo Sala, Vera M. Kalscheuer and Vania Broccoli doi:10.1038/ncb2566 The CDKL5 kinase is mutated in several neurodevelopmental disorders. Broccoli and colleagues find that CDKL5 regulates dendritic spine formation by phosphorylating the adhesion molecule NGL-1, which acts on synaptic contacts. They also show that neurons (derived from induced pluripotent stem cells) from patients carrying the CDKL5 mutation have aberrant dendritic spines, similarly to rodents with impaired CDKL5 function. Clathrin and phosphatidylinositol-4,5-bisphosphate regulate autophagic lysosome reformation   pp924 - 934 Yueguang Rong, Mei Liu, Liang Ma, Wanqing Du, Hanshuo Zhang, Yuan Tian, Zhen Cao, Ying Li, He Ren, Chuanmao Zhang, Lin Li, She Chen, Jianzhong Xi and Li Yu doi:10.1038/ncb2557 The last step in autophagy involves fusion of autophagosomes with lysosomes to generate autolysosomes. Through proteomics analysis and an RNAi screen, Yu and colleagues provide mechanistic insight into how lysosomes are regenerated from autolysosomes. Their analyses reveal a key role for clathrin and phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) in this process. Letters Top Mechanical force regulates integrin turnover in Drosophila in vivo    pp935 - 943 Mary Pines, Raibatak Das, Stephanie J. Ellis, Alexander Morin, Stefan Czerniecki, Lin Yuan, Markus Klose, Daniel Coombs and Guy Tanentzapf doi:10.1038/ncb2555 Tanentzapf and colleagues use genetic mutations that alter tensile force at the Drosophila myotendinous junction to demonstrate that mechanical force controls in vivo turnover of integrin and intracellular adhesion complexes. See also: News and Views by He & Montell Membrane bending by protein–protein crowding   pp944 - 949 Jeanne C. Stachowiak, Eva M. Schmid, Christopher J. Ryan, Hyoung Sook Ann, Darryl Y. Sasaki, Michael B. Sherman, Phillip L. Geissler, Daniel A. Fletcher and Carl C. Hayden doi:10.1038/ncb2561 Membrane deformation is necessary to generate endocytic vesicles, but the molecular mechanisms proposed to drive membrane bending are controversial. Stachowiak and Schmid et al. report that crowding of proteins at the membrane is sufficient to induce curvature in vitro. See also: News and Views by Kirchhausen The BBSome controls IFT assembly and turnaround in cilia   pp950 - 957 Qing Wei, Yuxia Zhang, Yujie Li, Qing Zhang, Kun Ling and Jinghua Hu doi:10.1038/ncb2560 Intraflagellar transport (IFT) particles are essential for the biogenesis and maintenance of cilia. They assemble at the cilium base and travel up and down the cilia, turning around at the tip, but the mechanisms that regulate these processes were not clear. Hu and colleagues reveal a role for the BBSome in IFT assembly and turnaround. See also: News and Views by Pedersen & Christensen Synthetic lethality between Rb, p53 and Dicer or miR-17–92 in retinal progenitors suppresses retinoblastoma formation   pp958 - 965 David Nittner, Irina Lambertz, Frederic Clermont, Pieter Mestdagh, Corinna Köhler, Søren Jensby Nielsen, Aart Jochemsen, Frank Speleman, Jo Vandesompele, Michael A. Dyer, Alexander Schramm, Johannes H. Schulte and Jean-Christophe Marine doi:10.1038/ncb2556 Marine and colleagues use mouse models to show that loss of Dicer or its downstream microRNA cluster miR-17–92 in retinal progenitors prevents retinoblastoma formation through a synthetic lethal interaction with Rb and p53 deficiency. Resource Top Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress   pp966 - 976 Johnny M. Tkach, Askar Yimit, Anna Y. Lee, Michael Riffle, Michael Costanzo, Daniel Jaschob, Jason A. Hendry, Jiongwen Ou, Jason Moffat, Charles Boone, Trisha N. Davis, Corey Nislow and Grant W. Brown doi:10.1038/ncb2549 Brown and colleagues take a systems-level approach to the DNA damage response by analysing the changes in localization and abundance of proteins in response to replication stress, using a budding yeast GFP fusion library and high-throughput microscopy. See also: News and Views by Thorpe & Rothstein Top Advertisement Online-only personal subscriptions now available to Nature Cell Biology and Nature Structural Molecular Biology For only 49 USD/29 GBP/29 EUR Subscribe now!   Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. 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