Nature Cell Biology contents: October 2012 Volume 14 Number 10, pp 977 - 1112

Advertisement Roche's X-tremeGENE Transfection Reagents Transfect efficiently with low cytotoxicity - proven in 275 different cell types...over 130 cancer cells. Free sample and protocols at www.x-tremegene.roche.com For life science research only. Not for use in diagnostic procedures. TABLE OF CONTENTS October 2012 Volume 14, Issue 10 Editorial Turning Points News and Views Research Highlights Articles Letters Advertisement Superior knockdown with next-generation shRNA New PLATINUM Select shRNA-mir collections developed by Dr. Greg Hannon at Cold Spring Harbor Laboratory are available exclusively from transOMIC technologies. Unrivaled potency with shRNA-specific shERWOOD algorithm, enhanced specificity, 100% guarantee on every shRNA-mir targeting your gene. Learn more. Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Don’t wash away your cells! Tecan's HydroSpeed™ Year-to-End Offer! • HydroSpeed plate washer offers extra gentle Cell Protection™ • wash settings • High cell recovery using tuneable aspiration settings • Anti-Clogging™ function for reliable ELISA washing Click for YOUR offer   Advertisement Nature Cell Biology Focus on Cell biology of metabolism The October 2012 issue of Nature Cell Biology presents a special collection of research and review articles that highlight recent advances in understanding metabolism and its importance for normal physiology and disease. www.nature.com/ncb/webfocus/metabolism   Editorial Top Science education reforms in the UK   p977 doi:10.1038/ncb2601 As children return to school at the end of the summer in the UK, planned reforms aim to increase their science and maths literacy. A comprehensive foundation in these essential subjects is necessary to ensure that the UK remains at the forefront of science and technology for decades to come. Turning Points Top Pathway discovery: The road to Ras and MAP kinase   p978 Chris Marshall doi:10.1038/ncb2587 News and Views Top Integrating insulin secretion and ER stress in pancreatic β-cells   pp979 - 981 Katleen Lemaire and Frans Schuit doi:10.1038/ncb2594 After food consumption, insulin-secreting pancreatic β-cells detect increased glucose and incretin hormones, and respond by releasing insulin. Wolfram syndrome 1, a protein that mitigates endoplasmic reticulum (ER) stress, is now shown to regulate insulin synthesis and release — revealing a molecular point of convergence between the ER stress and insulin release pathways. See also: Letter by Fonseca et al. Unanchoring integrins in focal adhesions   pp981 - 983 Johanna Ivaska doi:10.1038/ncb2592 Focal adhesions are large structures through which integrins and scaffold proteins link the actin cytoskeleton to the extracellular matrix. A detailed analysis of integrin dynamics now indicates that focal-adhesion-associated integrins constantly switch between active and immobilized, and unbound and free-diffusing states, with different fibronectin-binding integrin heterodimers showing distinct focal-adhesion dynamics. See also: Article by Rossier et al. Connecting membrane traffic to ESCRT and the final cut   pp983 - 985 Arnaud Echard doi:10.1038/ncb2598 The ESCRT (endosomal sorting complex required for transport) machinery is responsible for scission of the cytokinetic bridge that connects daughter cells at the end of mitosis. Specific endosomes are now found to mediate local bridge constriction and actin clearance in human cells, which contribute to the recruitment of ESCRT components at the abscission site. See also: Article by Schiel et al. Profilin phosphorylation as a VEGFR effector in angiogenesis   pp985 - 987 Michael Simons and Martin A. Schwartz doi:10.1038/ncb2596 Vascular endothelial growth factor (VEGF) signalling induces embryonic vascular development and angiogenesis in adult tissues. Direct phosphorylation of the actin-binding protein profilin by VEGF receptors is now shown to increase its affinity for actin, and to be essential for adult but not embryonic arteriogenesis. See also: Article by Fan et al. A potential link between obesity and neural stem cell dysfunction   pp987 - 989 Frederick J. Livesey doi:10.1038/ncb2599 Given the important role of the hypothalamus in regulating feeding and metabolism, there has been considerable interest in a possible function for hypothalamic stem cells in modulating body weight in health and disease. Mice given a high-fat diet develop inflammation in the hypothalamus and lose key types of neurons. It now appears that another effect of a high-fat diet is to reduce neural stem cell numbers, as well as their ability to make new neurons — effects that are associated with activation of the IKKβ/NF-κB pathway — thereby exacerbating the primary loss of neurons and resulting in altered feeding behaviour and obesity. See also: Article by Li et al. Cell Biology JOBS of the week Postdoctoral Fellow: Gene Regulation in Breast Cancer / Stem Cell Biology UC Department of Cancer and Cell Biology Tenure-Track Faculty Position in Cell, Molecular and Developmental Biology University of Rochester Department of Biology Chair of Stem Cell Biology and Associate Director The University of Edinburgh Senior Lecturer / Associate Professor in Histology and Cell Biology Umeå University, dept of Integrative Medical Biology Cell Biology Of RNA In Disease University of Ottawa / Université d'Ottawa More Science jobs from Cell Biology EVENT Dynamics of Immune Cell Communication Networks 11.10.12 NY, US More science events from Research Highlights Top Aurora A maintains embryonic stem cells | New ligases join the ubiquitylation cascade in repair | Mechanical control at cell-cell contacts | Hippo regulates mitochondrial size Advertisement Small Reactor - Big Results With CELLSTAR® CELLreactor™ • Innovative: 50 ml filter tube for suspension cultures • Safe: USP VI-certified 0.2 µm PTFE-coated capillary • membrane • Fast: Facilitates parallel experiments • Simple: Cultivation and harvest in one tube • Easy: Mixing by standard equipment Read more: www.gbo.com/bioscience   Articles Top Auxin regulates aquaporin function to facilitate lateral root emergence   pp991 - 998 Benjamin Péret, Guowei Li, Jin Zhao, Leah R. Band, Ute Voß, Olivier Postaire, Doan-Trung Luu, Olivier Da Ines, Ilda Casimiro, Mikaël Lucas, Darren M. Wells, Laure Lazzerini, Philippe Nacry, John R. King, Oliver E. Jensen, Anton R. Schäffner, Christophe Maurel and Malcolm J. Bennett doi:10.1038/ncb2573 Bennett and colleagues find that auxin modulates water uptake in Arabidopsis roots by negatively regulating the expression of water channel aquaporins to allow lateral root emergence. The functional importance of aquaporins is supported by a mathematical model that shows delayed lateral root emergence when aquaporin levels are perturbed, as well as by the effects observed after aquaporin overexpression or mutation. IKKβ/NF-κB disrupts adult hypothalamic neural stem cells to mediate a neurodegenerative mechanism of dietary obesity and pre-diabetes   pp999 - 1012 Juxue Li, Yizhe Tang and Dongsheng Cai doi:10.1038/ncb2562 Cai and colleagues show that the function of adult hypothalamic neural stem cells in mice is impaired following NF-κB activation associated with a chronic high-fat diet, resulting in development of obesity and neurodegenerative features. Mechanistically, NF-κB affects both Notch signalling and apoptosis in these cells. See also: News and Views by Livesey Insm1a-mediated gene repression is essential for the formation and differentiation of Müller glia-derived progenitors in the injured retina   pp1013 - 1023 Rajesh Ramachandran, Xiao-Feng Zhao and Daniel Goldman doi:10.1038/ncb2586 Goldman and colleagues report that the transcriptional repressor Insm1a is essential for retinal regeneration following injury in fish. Insm1a suppresses the expression of Ascl1a to promote Müller glial cells’ dedifferentiation at early stages of regeneration, and defines the regeneration zone by negatively regulating the expression of the heparin-binding EGF. It also halts the proliferation of retinal progenitors in the late stages of the process. Autophagy receptors link myosin VI to autophagosomes to mediate Tom1-dependent autophagosome maturation and fusion with the lysosome   pp1024 - 1035 David A. Tumbarello, Bennett J. Waxse, Susan D. Arden, Nicholas A. Bright, John Kendrick-Jones and Folma Buss doi:10.1038/ncb2589 Tumbarello, Buss and colleagues report that the motor protein myosin VI has an important role in autophagosome maturation. They show that myosin VI binds to autophagy adaptors to mediate delivery of endocytic cargo and endosomal membrane to autophagosomes, and promote autophagosome–lysosome fusion. Active Wnt proteins are secreted on exosomes   pp1036 - 1045 Julia Christina Gross, Varun Chaudhary, Kerstin Bartscherer and Michael Boutros doi:10.1038/ncb2574 The mechanisms that control intracellular Wnt trafficking and secretion are beginning to be unravelled. However, little is known about how Wnt proteins are transported once they reach extracellular space. Boutros and colleagues show that active Wnt proteins are secreted on exosomes from Drosophila and human cells, and provide insight into the cellular machinery that regulates their transport and release. Stimulus-dependent phosphorylation of profilin-1 in angiogenesis   pp1046 - 1056 Yi Fan, Abul Arif, Yanqing Gong, Jie Jia, Sandeepa M. Eswarappa, Belinda Willard, Arie Horowitz, Linda M. Graham, Marc S. Penn and Paul L. Fox doi:10.1038/ncb2580 Fox and colleagues report that VEGF-A stimulation of endothelial cells induces the phosphorylation of profilin by VEGFR2 and Src. This regulation promotes endothelial cell migration and angiogenesis in mice facing pathological conditions such as tissue wounding and ischaemic injury. See also: News and Views by Simons & Schwartz Integrins β1 and β3 exhibit distinct dynamic nanoscale organizations inside focal adhesions   pp1057 - 1067 Olivier Rossier, Vivien Octeau, Jean-Baptiste Sibarita, Cécile Leduc, Béatrice Tessier, Deepak Nair, Volker Gatterdam, Olivier Destaing, Corinne Albigès-Rizo, Robert Tampé, Laurent Cognet, Daniel Choquet, Brahim Lounis and Grégory Giannone doi:10.1038/ncb2588 Giannone and colleagues use super-resolution microscopy to analyse the nanoscale dynamic organization of talin and integrins β1 and β3 in focal adhesions. See also: News and Views by Ivaska FIP3-endosome-dependent formation of the secondary ingression mediates ESCRT-III recruitment during cytokinesis   pp1068 - 1078 John A. Schiel, Glenn C. Simon, Chelsey Zaharris, Julie Weisz, David Castle, Christine C. Wu and Rytis Prekeris doi:10.1038/ncb2577 During cytokinesis, the intercellular bridge connecting the mother and daughter cell is thinned by a process called secondary ingression before it is eventually severed in an ESCRT-III-dependent manner. Prekeris and colleagues report that FIP3-positive endosomes deliver p50RhoGAP and SCAMP2/3 proteins to the intercellular bridge, which promote actin depolymerization to decrease the bridge diameter and allow ESCRT-III binding. See also: News and Views by Echard Endocytosis of the seven-transmembrane RGS1 protein activates G-protein-coupled signalling in Arabidopsis    pp1079 - 1088 Daisuke Urano, Nguyen Phan, Janice C. Jones, Jing Yang, Jirong Huang, Jeffrey Grigston, J. Philip Taylor and Alan M. Jones doi:10.1038/ncb2568 In plants, the heterotrimeric G-protein α subunit is kept inactive by binding to the regulator of G protein signalling 1 (RGS1) protein. Jones and colleagues show that G-protein β and γ subunits recruit the WNK8 kinase to the plasma membrane, where WNK8 phosphorylates RGS1 and facilitates its internalization. This effect de-represses Gα signalling and is required for sugar signalling and cell proliferation. Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass   pp1089 - 1098 Lou K. Povlsen, Petra Beli, Sebastian A. Wagner, Sara L. Poulsen, Kathrine B. Sylvestersen, Jon W. Poulsen, Michael L. Nielsen, Simon Bekker-Jensen, Niels Mailand and Chunaram Choudhary doi:10.1038/ncb2579 In a quantitative proteomics approach, Mailand, Choudhary and colleagues characterize ultraviolet-regulated ubiquitylation sites and identify a role for double mono-ubiquitylation of PCNA-associated factor PAF15 in bypassing replication-blocking lesions in DNA. Advertisement The New BD FACSJazz™ Cell Sorter  Perfectly tuned cell sorting is now available with the new BD FACSJazz. Built on a proven, dependable platform, it may change the way you'll think of cell sorting with ease of operation, affordability, and a benchtop fit. Exceedingly capable performance whether as a soloist or part of your core lab ensemble. bdbiosciences.com/jazz   Letters Top Dll1+ secretory progenitor cells revert to stem cells upon crypt damage   pp1099 - 1104 Johan H. van Es, Toshiro Sato, Marc van de Wetering, Anna Lyubimova, Annie Ng Yee Nee, Alex Gregorieff, Nobuo Sasaki, Laura Zeinstra, Maaike van den Born, Jeroen Korving, Anton C. M. Martens, Nick Barker, Alexander van Oudenaarden and Hans Clevers doi:10.1038/ncb2581 Notch signalling in the intestinal crypt is modulated to drive commitment to the secretory fate. Clevers and colleagues find that cells expressing the Notch ligand DLL1 are intermediate secretory cells that can revert to Lgr5+ stem cells upon damage. Wolfram syndrome 1 and adenylyl cyclase 8 interact at the plasma membrane to regulate insulin production and secretion   pp1105 - 1112 Sonya G. Fonseca, Fumihiko Urano, Gordon C. Weir, Jesper Gromada and Mark Burcin doi:10.1038/ncb2578 Persistent ER stress in pancreatic β-cells contributes to the pathogenesis of type 2 diabetes. Fonseca and colleagues show that the ER membrane glycoprotein WFS1, which is mutated in people with Wolfram syndrome, has a known role in the ER stress response. It regulates insulin production and secretion in β-cells by associating with adenylyl cyclase 8 at the plasma membrane and generating cAMP. ER stress prevents WFS1 plasma membrane localization, attenuating cAMP production and insulin secretion. See also: News and Views by Lemaire & Schuit Top Advertisement The Encyclopedia of DNA Elements 30 papers published simultaneously in Nature, Genome Research and Genome Biology. 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