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The EMBO Journal

Cover image for Vol. 30 Issue 7

April 6, 2011

Volume 30, Issue 7

Pages 1185–1413

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      Compartmentalized regulation of autophagy regulators: fine-tuning AMBRA1 by Bcl-2 (pages 1185–1186)

      Sharon A Tooze and Patrice Codogno

      Version of Record online: 2 JUN 2010 | DOI: 10.1038/emboj.2011.75

      AMBRA1 and Bcl-2 both interact with Beclin 1 and control autophagy as a positive or negative regulator, respectively. A paper in this issue reveals an interaction between AMBRA1 and Bcl-2 at the mitochondrial outer membrane that is relieved upon induction of autophagy or apoptosis allowing AMBRA1 to activate Beclin 1.

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      Immune synapses: mitochondrial morphology matters (pages 1187–1189)

      Christian Junker and Markus Hoth

      Version of Record online: 2 JUN 2010 | DOI: 10.1038/emboj.2011.72

      Mitochondria accumulate at the immune synapse (IS), but it is not clear how this is achieved. Francisco Sánchez-Madrid and colleagues report in this issue of The EMBO Journal that the mitochondrial fission factor DRP1, which regulates mitochondria morphology, also controls mitochondrial localization at the IS and thereby modulates IS formation and downstream signalling.

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      Clamping the clamp of RNA polymerase (pages 1190–1191)

      Vladimir Svetlov and Evgeny Nudler

      Version of Record online: 2 JUN 2010 | DOI: 10.1038/emboj.2011.76

      This article highlights the general mechanistic implications for transcriptional elongation based on the crystal structure describing Spt4/5 bound to the RNA polymerase clamp domain from the Cramer lab.

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      Some like it hot: decoding neurotransmission in the worm's thermotaxis circuit (pages 1192–1194)

      Evan L Ardiel and Catharine H Rankin

      Version of Record online: 2 JUN 2010 | DOI: 10.1038/emboj.2011.71

      A paper in this issue of the EMBO Journal examines the neural circuit controlling locomotion in thermal gradients in Caenorhabditis elegans. Opposing transmission from two thermosensory neurons, AFD and AWC, determines temperature preference.

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      Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy (pages 1195–1208)

      Flavie Strappazzon, Matteo Vietri-Rudan, Silvia Campello, Francesca Nazio, Fulvio Florenzano, Gian Maria Fimia, Mauro Piacentini, Beth Levine and Francesco Cecconi

      Version of Record online: 25 FEB 2011 | DOI: 10.1038/emboj.2011.49

      AMBRA1 is a positive regulator of BECLIN 1- dependent autophagy. Under basal conditions, AMBRA-1 is sequestered by Bcl-2 at the mitochondria. Upon induction of autophagy or apoptosis, AMBRA-1 is released to interact with BECLIN-1.

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      Ca2+ induces clustering of membrane proteins in the plasma membrane via electrostatic interactions (pages 1209–1220)

      Felipe E Zilly, Nagaraj D Halemani, David Walrafen, Luis Spitta, Arne Schreiber, Reinhard Jahn and Thorsten Lang

      Version of Record online: 1 MAR 2011 | DOI: 10.1038/emboj.2011.53

      This study reveals that calcium influx through voltage-gated calcium channels triggers reversible redistribution and clustering of plasma membrane proteins.

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      Substrate specificity and ion coupling in the Na+/betaine symporter BetP (pages 1221–1229)

      Camilo Perez, Caroline Koshy, Susanne Ressl, Sascha Nicklisch, Reinhard Krämer and Christine Ziegler

      Version of Record online: 1 MAR 2011 | DOI: 10.1038/emboj.2011.46

      BetP is an Na+-coupled betaine transporter that is involved in the osmotic stress response. Based on a point mutant that converts BetP into an H+-coupled choline transporter, this study characterizes the coupling mechanism between the substrate and the co-transported ion.

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      Structural basis for the slow dynamics of the actin filament pointed end (pages 1230–1237)

      Akihiro Narita, Toshiro Oda and Yuichiro Maéda

      Version of Record online: 4 MAR 2011 | DOI: 10.1038/emboj.2011.48

      Actin filaments have highly dynamic barbed ends and slowly turning over pointed ends. This cryo-electron microscopy analysis provides insight into the structural basis of these different kinetic properties of the two ends.

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      The mitochondrial fission factor dynamin-related protein 1 modulates T-cell receptor signalling at the immune synapse (pages 1238–1250)

      Francesc Baixauli, Noa B Martín-Cófreces, Giulia Morlino, Yolanda R Carrasco, Carmen Calabia-Linares, Esteban Veiga, Juan M Serrador and Francisco Sánchez-Madrid

      Version of Record online: 15 FEB 2011 | DOI: 10.1038/emboj.2011.25

      During antigen presentation, T cells relocalize organelles, adhesion and signalling components to the immunological synapse (IS). This study shows that the localization of mitochondria to the IS is regulated by the mitochondrial fission factor Drp1 and that this is important for T-cell activation.

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      Conformational changes underlying calcium/calmodulin-dependent protein kinase II activation (pages 1251–1262)

      Laurel Hoffman, Richard A Stein, Roger J Colbran and Hassane S Mchaourab

      Version of Record online: 22 FEB 2011 | DOI: 10.1038/emboj.2011.40

      Based on spin label and EPR spectroscopy, this study provides a plausible model for activation and autophosphorylation of the ubiquitous signalling molecule CaMKII. The emerging dynamic picture informs earlier crystal structure-based interpretations and seems consistent with the majority of available experimental data.

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      TGF-β signalling is mediated by two autonomously functioning TβRI:TβRII pairs (pages 1263–1276)

      Tao Huang, Laurent David, Valentín Mendoza, Yong Yang, Maria Villarreal, Keya De, LuZhe Sun, Xiaohong Fang, Fernando López-Casillas, Jeffrey L Wrana and Andrew P Hinck

      Version of Record online: 18 MAR 2011 | DOI: 10.1038/emboj.2011.54

      In this study, Andrew Hinck and colleagues differentiate TGF-β from BMP receptor complexes. Based on various biochemical techniques they report a functional hetero-dimeric TGF-β complex that contrasts the hetero-tetrameric composition of active BMP receptors.

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      The RSC chromatin remodelling enzyme has a unique role in directing the accurate positioning of nucleosomes (pages 1277–1288)

      Christian J Wippo, Lars Israel, Shinya Watanabe, Andreas Hochheimer, Craig L Peterson and Philipp Korber

      Version of Record online: 22 FEB 2011 | DOI: 10.1038/emboj.2011.43

      The molecular mechanisms involved in establishing nucleosome positions in vivo are not well understood. Here, RSC is specifically required for moving nucleosomes from their intrinsically preferred in vitro reconstituted locations to their physiologically relevant positions.

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      Degringolade, a SUMO-targeted ubiquitin ligase, inhibits Hairy/Groucho-mediated repression (pages 1289–1301)

      Mona Abed, Kevin C Barry, Dorit Kenyagin, Bella Koltun, Taryn M Phippen, Jeffrey J Delrow, Susan M Parkhurst and Amir Orian

      Version of Record online: 22 FEB 2011 | DOI: 10.1038/emboj.2011.42

      The transcriptional repressor Hairy is required for embryonic segmentation and adult peripheral nervous system specification in Drosophila. Here, the SUMO-targeted ubiquitin ligase, Degringolade, negatively regulates Hairy activity by regulating recruitment of the corepressor Groucho.

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      Architecture of the RNA polymerase–Spt4/5 complex and basis of universal transcription processivity (pages 1302–1310)

      Fuensanta W Martinez-Rucobo, Sarah Sainsbury, Alan CM Cheung and Patrick Cramer

      Version of Record online: 8 MAR 2011 | DOI: 10.1038/emboj.2011.64

      Spt5 and NusG play a conserved role in stimulating RNA polymerase II transcription elongation and processivity. Here, the crystal structure of Spt4/5 bound to the RNA polymerase clamp domain reveals that the factor binds above DNA and RNA in the active centre cleft preventing premature dissociation of the polymerase.

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      Anti-proliferative protein Tob negatively regulates CPEB3 target by recruiting Caf1 deadenylase (pages 1311–1323)

      Nao Hosoda, Yuji Funakoshi, Masato Hirasawa, Ryota Yamagishi, Yukako Asano, Ryu Miyagawa, Koichi Ogami, Masafumi Tsujimoto and Shin-ichi Hoshino

      Version of Record online: 18 FEB 2011 | DOI: 10.1038/emboj.2011.37

      Shortening of the 3′ poly(A) tail by deadenylation promotes mRNA decay. Here, the authors show that the anti-proliferative protein Tob binds to the cytoplasmic polyadenylation element-binding protein CPEB3 and recruits the deadenylase Caf1 to target mRNAs to promote deadenylation and mRNA turnover.

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      Repression of VEGFA by CA-rich element-binding microRNAs is modulated by hnRNP L (pages 1324–1334)

      Faegheh Jafarifar, Peng Yao, Sandeepa M Eswarappa and Paul L Fox

      Version of Record online: 22 FEB 2011 | DOI: 10.1038/emboj.2011.38

      There is increasing evidence of interplay between miRNAs and RNA-binding proteins in regulating protein expression. Here, the hypoxia-induced relocalization of heterogeneous nuclear ribonucleoprotein L (hnRNP L) relieves miRNA-mediated repression of the VEGFA mRNA by binding to the 3′-UTR region that is targeted by several miRNAs.

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      Cas3 is a single-stranded DNA nuclease and ATP-dependent helicase in the CRISPR/Cas immune system (pages 1335–1342)

      Tomas Sinkunas, Giedrius Gasiunas, Christophe Fremaux, Rodolphe Barrangou, Philippe Horvath and Virginijus Siksnys

      Version of Record online: 22 FEB 2011 | DOI: 10.1038/emboj.2011.41

      Cas3 is an essential protein of unknown function required for CRISPR-based bacteriophage immunity in bacteria. Here, the biochemical activities of Cas3 are demonstrated and mechanistic implications for immunity are discussed.

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      Viral factor TAV recruits TOR/S6K1 signalling to activate reinitiation after long ORF translation (pages 1343–1356)

      Mikhail Schepetilnikov, Kappei Kobayashi, Angèle Geldreich, Carole Caranta, Christophe Robaglia, Mario Keller and Lyubov A Ryabova

      Version of Record online: 22 FEB 2011 | DOI: 10.1038/emboj.2011.39

      The polycistronic mRNA of Cauliflower mosaic virus is translated via a translation reinitiation mechanism that depends on the viral protein TAV and the host factor RISP. This study reveals a physical interaction between TAV and TOR kinase and identifies RISP as a relevant TOR substrate.

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      The unfolded protein response transducer IRE1α prevents ER stress-induced hepatic steatosis (pages 1357–1375)

      Kezhong Zhang, Shiyu Wang, Jyoti Malhotra, Justin R Hassler, Sung Hoon Back, Guohui Wang, Lin Chang, Wenbo Xu, Hongzhi Miao, Roberta Leonardi, Y Eugene Chen, Suzanne Jackowski and Randal J Kaufman

      Version of Record online: 15 MAR 2011 | DOI: 10.1038/emboj.2011.52

      Ire1α is an important stress sensor in the unfolded protein response. The present study characterizes its essential function in liver lipid homeostasis based on hepatocyte-specific Ire1α knockout mice.

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      Bidirectional regulation of thermotaxis by glutamate transmissions in Caenorhabditis elegans (pages 1376–1388)

      Noriyuki Ohnishi, Atsushi Kuhara, Fumiya Nakamura, Yoshifumi Okochi and Ikue Mori

      Version of Record online: 8 FEB 2011 | DOI: 10.1038/emboj.2011.13

      This paper provides a molecular and genetic analysis of the neural circuitry that regulates the migration of Caenorhabditis elegans towards either warmer or colder temperature and reveals an important role of glutamate signalling in this process.

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      Myelin suppresses axon regeneration by PIR-B/SHP-mediated inhibition of Trk activity (pages 1389–1401)

      Yuki Fujita, Shota Endo, Toshiyuki Takai and Toshihide Yamashita

      Version of Record online: 1 MAR 2011 | DOI: 10.1038/emboj.2011.55

      Myelin inhibits neurite growth and regeneration via the immunoglobulin-like receptor PIR-B. PIR-B binds to Trk receptors leading to its dephosphorylation and inactivation by recruiting the phosphatases SHP-1 and SHP-2.

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      Evidence that metabolism and chromosome copy number control mutually exclusive cell fates in Bacillus subtilis (pages 1402–1413)

      Yunrong Chai, Thomas Norman, Roberto Kolter and Richard Losick

      Version of Record online: 15 FEB 2011 | DOI: 10.1038/emboj.2011.36

      The epigenetic switch between Bacillus biofilm formation and sporulation programs is found to depend on differential affinities of a response regulator for activating and repressive gene regulation sequences, and on ploidy levels of a repressor–antirepressor pair possibly constituting a chromosome-counting mechanism.