Nature Cell Biology contents: October 2013 Volume 15 Number 10, pp 1133 - 1260

Advertisement Roche's X-tremeGENE Transfection Reagents Efficiently transfect difficult cells, including more than 100 cancer cell lines. 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 2013 Volume 15, Issue 10 Turning Points Obituary News and Views Articles Letters Corrigenda Advertisement PhotoFluor LM-75  World's first direct-mounted metal halide light source for fluorescence imaging. Very quiet operation. No liquid light guide. Low up-front cost and overall cost of ownership. Long lamp life. No user alignment. Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Frontiers in Cell and Developmental Biology is a new open access journal launching in October 2013! Our open access platform and research network enables you make the most of your research and valuable professional network. Connect to colleagues, increase your impact and benefit from a 30% increase in downloads to any publication you link to your profile. Over 100,000 researchers are already here - we are just waiting for you: register today   Turning Points Top Making a knockout mouse: From stem cells to embryos   p1133 Janet Rossant doi:10.1038/ncb2850 Obituary Top Tony Pawson 1952-2013   p1134 Carl-Henrik Heldin and John Scott doi:10.1038/ncb2854 News and Views Top TSC on the peroxisome controls mTORC1   pp1135 - 1136 Don Benjamin and Michael N. Hall doi:10.1038/ncb2849 mTOR is a central controller that integrates many inputs to regulate cell growth and ensure cellular homeostasis. The mTORC1 inhibitor TSC (tuberous sclerosis complex) on the peroxisome is found to inhibit mTORC1 in response to endogenous reactive oxygen species. Thus, mTOR may avoid confounding different inputs by sensing them at different cellular locations. See also: Article by Zhang et al. Q-bodies monitor the quinary state of the protein fold   pp1137 - 1139 Daniela Martino Roth and William E. Balch doi:10.1038/ncb2857 Cytoplasmic compartments containing misfolded proteins targeted for degradation, named Q-bodies, have been identified. Q-body formation is a dynamic process that actively manages the metastable state of the protein fold through small heat shock proteins and the Hsp70-Hsp90-Hsp110 proteostasis system to promote cellular fitness under both physiological and stress conditions. See also: Article by Escusa-Toret et al. SON sheds light on RNA splicing and pluripotency   pp1139 - 1140 Ilana Livyatan and Eran Meshorer doi:10.1038/ncb2851 The role of RNA splicing in the regulation of stem cell properties has remained largely unexplored. The splicing-associated protein SON is now shown to be necessary for embryonic stem cell maintenance, by influencing the splicing of pluripotency regulators. See also: Article by Lu et al. Cell Biology JOBS of the week Faculty Positions Available in the Department of Cell and Molecular Biology Feinberg School of Medicine, Northwestern University Faculty Appointment in Cell Biology Duke University Medical Center Assistant Professor – Cell & Developmental Biology University of Toronto Post Doctoral Research Position in Immune Recovery After Hematopoeitic Stem Cell Transplantation University of Minnesota - Twin Cities Postdoctoral Position in Cell Biology / Molecular Neuroscience University of Massachusett Medical School More Science jobs from Cell Biology EVENT Cell Biology of Yeasts 5th - 9th November 2013 Cold Spring Harbor, USA More science events from Advertisement Save 30%: Enhanced BD Horizon™ Brilliant Violet™ Reagents  Innovative new formulations of BD Horizon™ Brilliant Violet™ polymer conjugates are now available. Brighter than traditional dyes, these reagents can help you to resolve rare and dim cell populations, revealing nature's secrets with unprecedented clarity. Request a free sample or take 30% off purchases.  bdbiosciences.com/go/brilliant   Articles Top SON connects the splicing-regulatory network with pluripotency in human embryonic stem cells   pp1141 - 1152 Xinyi Lu, Jonathan Göke, Friedrich Sachs, Pierre-Étienne Jacques, Hongqing Liang et al. doi:10.1038/ncb2839 Ng and colleagues show that the spliceosome-associated factor SON is essential for the maintenance of pluripotency and the survival of human embryonic stem cells. Using genome-wide RNA profiling to identify SON-regulated transcripts, they find that it modulates splicing of transcripts of pluripotency regulators such as OCT4, PRDM14, E4F1 and MED24. See also: News and Views by Livyatan & Meshorer MicroRNA-205 controls neonatal expansion of skin stem cells by modulating the PI(3)K pathway   pp1153 - 1163 Dongmei Wang, Zhaojie Zhang, Evan O’Loughlin, Li Wang, Xiying Fan et al. doi:10.1038/ncb2827 Skin stem cells are amplified in early development. Yi and colleagues found that miR-205 promotes neonatal skin stem cell expansion by directly targeting negative regulators of PI(3)K–Akt signalling to maintain proliferation. In vivo reprogramming of astrocytes to neuroblasts in the adult brain   pp1164 - 1175 Wenze Niu, Tong Zang, Yuhua Zou, Sanhua Fang, Derek K. Smith et al. doi:10.1038/ncb2843 Adult differentiated cells can be reprogrammed to lineage-restricted proliferating neural precursors in vitro. Zhang and colleagues show that the transcription factor SOX2 is sufficient to reprogram resident astrocytes in the mouse brain to neuroblasts that can proliferate and differentiate following treatment with histone deacetylase inhibitors and differentiating factors BDNF and noggin. Riquiqui and Minibrain are regulators of the Hippo pathway downstream of Dachsous   pp1176 - 1185 Joffrey L. Degoutin, Claire C. Milton, Eefang Yu, Marla Tipping, Floris Bosveld et al. doi:10.1038/ncb2829 In the Hippo pathway, the atypical cadherins Fat and Dachsous modulate tissue growth, planar cell polarity and tissue patterning by acting on Wts kinase, which inhibits the transcription effects of Yki. Harvey and colleagues have identified two regulators of Hippo, the WD40 protein Riquiqui and the DYRK kinase Minibrain, that act downstream of Dachsous to inhibit Wts and promote Yki-dependent tissue growth. A tuberous sclerosis complex signalling node at the peroxisome regulates mTORC1 and autophagy in response to ROS   pp1186 - 1196 Jiangwei Zhang, Jinhee Kim, Angela Alexander, Shengli Cai, Durga Nand Tripathi et al. doi:10.1038/ncb2822 Reactive oxygen species inhibit mTORC1 signalling, but the subcellular localization of this event has been unclear. Walker and colleagues show that the tuberous sclerosis complex (TSC) is located at the peroxisome, where it functions as a Rheb GTPase-activator protein to suppress mTORC1 and induce autophagy. They also show that disease-associated mutations in TCS2 display impaired peroxisome localization and mTORC1 repression. See also: News and Views by Benjamin & Hall Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells   pp1197 - 1205 Charleen T. Chu, Jing Ji, Ruben K. Dagda, Jian Fei Jiang, Yulia Y. Tyurina et al. doi:10.1038/ncb2837 How injured mitochondria are targeted for autophagic degradation is not well understood. Chu and colleagues find that pro-mitophagy stimuli induce externalization of cardiolipin to the outer mitochondrial membrane of neuronal cells, and find that this is required for binding of the autophagy protein LC3 to mitochondria and mitophagy. PtdIns(3)P-bound UVRAG coordinates Golgi–ER retrograde and Atg9 transport by differential interactions with the ER tether and the beclin 1 complex   pp1206 - 1219 Shanshan He, Duojiao Ni, Binyun Ma, Joo-Hyung Lee, Tian Zhang et al. doi:10.1038/ncb2848 ER–Golgi transport and autophagy are tightly connected. Liang and colleagues find that UVRAG binds to PtdIns(3)P to localize it to the ER, from where, under normal conditions, it regulates the transport of COPI cargo transfer to the ER and Golgi integrity, but from where, following autophagy induction, it dissociates to modulate ATG9 transfer to autophagosomes. The deubiquitylase USP33 discriminates between RALB functions in autophagy and innate immune response   pp1220 - 1230 Michal Simicek, Sam Lievens, Mathias Laga, Dmytro Guzenko, Vasily N. Aushev et al. doi:10.1038/ncb2847 The RAS-like GTPase RALB mediates cellular responses to nutrient availability or viral infection by engaging two distinct exocyst complex proteins: EXO84 to modulate autophagy and SEC5 to regulate innate immune signalling. Sablina and colleagues find that whereas ubiquitylation of RALB at K47 promotes its interaction with SEC5, the de-ubiquitylase USP33 switches RALB to the EXO84–beclin complex to promote autophagy during nutrient starvation. Spatial sequestration of misfolded proteins by a dynamic chaperone pathway enhances cellular fitness during stress   pp1231 - 1243 Stéphanie Escusa-Toret, Willianne I. M. Vonk and Judith Frydman doi:10.1038/ncb2838 Quality control of misfolded proteins is thought to involve proteasome-dependent degradation or, if this fails, sequestration into inclusion bodies. Frydman and colleagues reveal the existence of endoplasmic-reticulum-associated structures, termed Q-bodies, that concentrate misfolded proteins in a chaperone-dependent manner before degradation. See also: News and Views by Roth & Balch Letters Top Early role for IL-6 signalling during generation of induced pluripotent stem cells revealed by heterokaryon RNA-Seq   pp1244 - 1252 Jennifer J. Brady, Mavis Li, Silpa Suthram, Hui Jiang, Wing H. Wong et al. doi:10.1038/ncb2835 Blau and colleagues show that non-dividing heterokaryons between mouse embryonic stem cells and human fibroblasts, in which human nuclei reprogram to a more embryonic state, can be used to identify signalling pathways involved in reprogramming. They delineate that IL-6 signalling and JAK/STAT target kinase Pim1 signalling are induced during this reprogramming, and that they increase the efficiency of factor-mediated reprogramming to induced pluripotent stem cell status. A nuclear F-actin scaffold stabilizes ribonucleoprotein droplets against gravity in large cells   pp1253 - 1259 Marina Feric and Clifford P. Brangwynne doi:10.1038/ncb2830 Actin is abundant in the nuclei of oocytes but its role has been unclear. Feric and Brangwynne find that actin forms a network that prevents the sedimentation of RNA and protein bodies caused by gravitational forces. Corrigenda Top Stromal-epithelial crosstalk regulates kidney progenitor cell differentiation   p1260 Amrita Das, Shunsuke Tanigawa, Courtney M. Karner, Mei Xin, Lawrence Lum et al. doi:10.1038/ncb2853 Functional interplay between the DNA-damage-response kinase ATM and ARF tumour suppressor protein in human cancer   p1260 Georgia Velimezi, Michalis Liontos, Konstantinos Vougas, Theodoros Roumeliotis, Jirina Bartkova et al. doi:10.1038/ncb2852 Top Advertisement Nature Insight Tumour Heterogeneity Tumour heterogeneity has important clinical implications, as it can explain therapeutic resistance, but also point to novel strategies to effectively treat cancers in a more personalised manner.  Access the Insight free online for three months    Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. 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