Funding boom or bust? - p227

doi:10.1038/ncb0309-227

The impact of the continuing economic woes on science funding remains uncertain. Surprisingly, the crisis may actually reinvigorate research. Investment in science and education is a prerequisite not only for emergence from the economic downward spiral, but also for addressing pressing global needs.

Full Text - Funding boom or bust? | PDF (180 KB) - Funding boom or bust?

Many roads to maturity: microRNA biogenesis pathways and their regulation - pp228 - 234

Julia Winter, Stephanie Jung, Sarina Keller, Richard I. Gregory & Sven Diederichs

doi:10.1038/ncb0309-228

A variety of microRNA biosynthesis pathways have emerged. The review discusses their impact on post-transcriptional microRNA regulation during tumour development with a particular focus on post-transcriptional maturation mechanisms specific to individual microRNAs.

Abstract - | Full Text - Many roads to maturity: microRNA biogenesis pathways and their regulation | PDF (856 KB) - Many roads to maturity: microRNA biogenesis pathways and their regulation

Prions tunnel between cells - pp235 - 236

Hans-Hermann Gerdes

doi:10.1038/ncb0309-235

Prions are abnormal isoforms of host proteins that are the infectious agents in certain mammalian neurodegenerative diseases. How prions travel from their peripheral entry sites to the brain where they cause disease is poorly understood. A new study finds that tunnelling nanotubes are important for the intercellular transfer of prions during neuroinvasion.

Full Text - Prions tunnel between cells | PDF (220 KB) - Prions tunnel between cells

See also: Letter by Gousset et al.

When you are Dishevelled, fat is good and acid is bad! - pp237 - 239

François Schweisguth

doi:10.1038/ncb0309-237

Frizzled receptors regulate cell fate decisions and planar cell polarity by means of distinct intracellular effectors. The choice between these two signalling outputs may involve a pH-dependent interaction between Dishevelled and negatively charged lipids at the plasma membrane.

Full Text - When you are Dishevelled, fat is good and acid is bad! | PDF (241 KB) - When you are Dishevelled, fat is good and acid is bad!

Breast cancer quality control - pp239 - 241

Cam Patterson & Sarah Ronnebaum

doi:10.1038/ncb0309-239

Tumorigenesis is regulated by several mechanisms including signalling, transcription and DNA replication. Now a cytoplasmic protein quality-control pathway is implicated in the suppression of breast cancer cell growth, suggesting a new role for quality-control mechanisms in suppressing cells with malignant potential.

Full Text - Breast cancer quality control | PDF (279 KB) - Breast cancer quality control

See also: Letter by Kajiro et al.

Prions remodel gene expression in yeast - pp241 - 243

Mick F. Tuite & Brian S. Cox

doi:10.1038/ncb0309-241

Epigenetic mechanisms participate in the regulation of gene transcription in eukaryotes. Two studies in yeast have revealed an additional mechanism for controlling global gene transcription that is based on an inherited self-perpetuating change in the conformation of two different components of key transcriptional regulatory complexes.

Full Text - Prions remodel gene expression in yeast | PDF (278 KB) - Prions remodel gene expression in yeast

See also: Letter by Patel et al.

How to grow a bud: an importin acts in asymmetric division - pp243 - 245

David S. Goldfarb

doi:10.1038/ncb0309-243

The growth of daughter cells in budding yeast is a classic model for investigating mechanisms involved in asymmetric cell division. An unexpected collaboration between the DEAD-box protein Dbp5 and the nuclear transport receptor Kap104 controls localized protein synthesis at the bud tip during mitosis.

Full Text - How to grow a bud: an importin acts in asymmetric division | PDF (555 KB) - How to grow a bud: an importin acts in asymmetric division

See also: Letter by van den Bogaart et al.

Research highlights - p246

doi:10.1038/ncb0309-246

Full Text - Research highlights | PDF (173 KB) - Research highlights

Requirement for Nudel and dynein for assembly of the lamin B spindle matrix - pp247 - 256

Li Ma, Ming-Ying Tsai, Shusheng Wang, Bingwen Lu, Rong Chen, John R. Yates III, Xueliang Zhu & Yixian Zheng

doi:10.1038/ncb1832

Lamin B is a component of a membranous matrix thought to be essential for spindle assembly. The dynein motor and its interacting protein Nudel are required for the recruitment of lamin B to the spindle matrix.

Abstract - | Full Text - Requirement for Nudel and dynein for assembly of the lamin B spindle matrix | PDF (3,116 KB) - Requirement for Nudel and dynein for assembly of the lamin B spindle matrix | Supplementary information

Myocardin-related transcription factors and SRF are required for cytoskeletal dynamics and experimental metastasis - pp257 - 268

Souhila Medjkane, Cristina Perez-Sanchez, Cedric Gaggioli, Erik Sahai & Richard Treisman

doi:10.1038/ncb1833

By preventing G-actin accumulation, Rho-GTPase promotes the transcriptional activity of myocardin-related transcription factors (MRTFs), known co-factors of serum response factor (SRF). Rho-dependent MRTF expression is required for injected metastatic cell lines to colonize the lung.

Abstract - | Full Text - Myocardin-related transcription factors and SRF are required for cytoskeletal dynamics and experimental metastasis | PDF (4,268 KB) - Myocardin-related transcription factors and SRF are required for cytoskeletal dynamics and experimental metastasis | Supplementary information

NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote meiotic spindle rotation independently of cortical LIN-5/GPR/G - pp269 - 277

Monique van der Voet, Christian W. H. Berends, Audrey Perreault, Tu Nguyen-Ngoc, Pierre Gönczy, Marc Vidal, Mike Boxem & Sander van den Heuvel

doi:10.1038/ncb1834

LIN-5 acts at the cortex with Ga to control spindle positioning but is also localized at spindle poles. The LIN-5 interacting protein ASPM-1 and calmodulin are required for its recruitment to spindle poles and the LIN-5/ASPM-1/calmodulin complex regulates meiotic spindle positioning.

First Paragraph - | Full Text - NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote meiotic spindle rotation independently of cortical LIN-5/GPR/G | PDF (2,690 KB) - NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote meiotic spindle rotation independently of cortical LIN-5/GPR/G | Supplementary information

An ATM- and ATR-dependent checkpoint inactivates spindle assembly by targeting CEP63 - pp278 - 285

Eloise Smith, Donniphat Dejsuphong, Alessia Balestrini, Martin Hampel, Christof Lenz, Shunichi Takeda, Alessandro Vindigni & Vincenzo Costanzo

doi:10.1038/ncb1835

Double-strand breaks in DNA activate the kinases ATM and ATR, which block entry into mitosis. ATM and ATR also delay mitotic progression by controlling spindle assembly in Xenopus egg extracts through the phosphorylation of the centrosomal protein CEP63, leading to its delocalization from the centrosome.

First Paragraph - | Full Text - An ATM- and ATR-dependent checkpoint inactivates spindle assembly by targeting CEP63 | PDF (2,633 KB) - An ATM- and ATR-dependent checkpoint inactivates spindle assembly by targeting CEP63 | Supplementary information

Electrochemical cues regulate assembly of the Frizzled/Dishevelled complex at the plasma membrane during planar epithelial polarization - pp286 - 294

Matias Simons, William J. Gault, Daniel Gotthardt, Rajeev Rohatgi, Thomas J. Klein, Youming Shao, Ho-Jin Lee, Ai-Luen Wu, Yimin Fang, Lisa M. Satlin, Julian T. Dow, Jie Chen, Jie Zheng, Michael Boutros & Marek Mlodzik

doi:10.1038/ncb1836

A genome-wide RNAi screen reveals the importance of local pH regulation during planar epithelial polarization. The plasma membrane association of the planar cell polarity components Dishevelled/Frizzled depends on the activity of the Na⁺/H⁺ membrane exchanger Nhe2.

First Paragraph - | Full Text - Electrochemical cues regulate assembly of the Frizzled/Dishevelled complex at the plasma membrane during planar epithelial polarization | PDF (3,193 KB) - Electrochemical cues regulate assembly of the Frizzled/Dishevelled complex at the plasma membrane during planar epithelial polarization | Supplementary information

Chfr is linked to tumour metastasis through the downregulation of HDAC1 - pp295 - 302

Young Mi Oh, Young Eun Kwon, Joo Mi Kim, Sung Jun Bae, Bo Keun Lee, Soon Ji Yoo, Chin Ha Chung, Raymond J. Deshaies & Jae Hong Seol

doi:10.1038/ncb1837

The ubiquitin ligase Chfr polyubiquitylates the histone deacetylase Hdac1, resulting in its proteolysis and the concomitant upregulation of metastasis suppressors, which may provide a molecular explanation for the known effects of Chfr on tumour progression.

First Paragraph - | Full Text - Chfr is linked to tumour metastasis through the downregulation of HDAC1 | PDF (2,069 KB) - Chfr is linked to tumour metastasis through the downregulation of HDAC1 | Supplementary information

Intercellular transfer to signalling endosomes regulates an ex vivo bone marrow niche - pp303 - 311

Jennifer M. Gillette, Andre Larochelle, Cynthia E. Dunbar & Jennifer Lippincott-Schwartz

doi:10.1038/ncb1838

Live-cell imaging shows that haematopoietic progenitor cells contact osteoblasts through a specialized membrane domain that is consequently internalized by osteoblasts. This results in downregulation of Smad signalling and the production of chemokines by osteoblasts that stimulate haematopoietic progenitor cell homing to bone marrow.

First Paragraph - | Full Text - Intercellular transfer to signalling endosomes regulates an ex vivo bone marrow niche | PDF (1,688 KB) - Intercellular transfer to signalling endosomes regulates an ex vivo bone marrow niche | Supplementary information

The ubiquitin ligase CHIP acts as an upstream regulator of oncogenic pathways - pp312 - 319

Masashi Kajiro, Ryuichi Hirota, Yuka Nakajima, Kaori Kawanowa, Kae So-ma, Ichiaki Ito, Yuri Yamaguchi, Sho-hei Ohie, Yasuhito Kobayashi, Yuko Seino, Miwako Kawano, Yoh-ichi Kawabe, Hiroyuki Takei, Shin-ichi Hayashi, Masafumi Kurosumi, Akiko Murayama, Keiji Kimura & Junn Yanagisawa

doi:10.1038/ncb1839

The ubiquitin ligase CHIP suppresses tumour growth and metastasis in breast cancer, and its expression inversely correlates with malignancy. The role of CHIP in cancer depends on degradation of the transcriptional co-activator SRC-3, which regulates expression of Smad and Twist.

First Paragraph - | Full Text - The ubiquitin ligase CHIP acts as an upstream regulator of oncogenic pathways | PDF (3,022 KB) - The ubiquitin ligase CHIP acts as an upstream regulator of oncogenic pathways | Supplementary information

See also: News and Views by Patterson & Ronnebaum

Oct1 loss of function induces a coordinate metabolic shift that opposes tumorigenicity - pp320 - 327

Arvind Shakya, Robert Cooksey, James E. Cox, Victoria Wang, Donald A. McClain & Dean Tantin

doi:10.1038/ncb1840

Cancer cells characteristically undergo a shift from oxidative to glycolytic metabolism. Loss of the transcription factor Oct1 opposes tumorigenicity by inducing a coordinate metabolic shift from glucose metabolism to increased mitochondrial activity and amino acid oxidation.

First Paragraph - | Full Text - Oct1 loss of function induces a coordinate metabolic shift that opposes tumorigenicity | PDF (2,296 KB) - Oct1 loss of function induces a coordinate metabolic shift that opposes tumorigenicity | Supplementary information

Prions hijack tunnelling nanotubes for intercellular spread - pp328 - 336

Karine Gousset, Edwin Schiff, Christelle Langevin, Zrinka Marijanovic, Anna Caputo, Duncan T. Browman, Nicolas Chenouard, Fabrice de Chaumont, Angelo Martino, Jost Enninga, Jean-Christophe Olivo-Marin, Daniela Männel & Chiara Zurzolo

doi:10.1038/ncb1841

Tunnelling nanotubes provide a means of intercellular communication. They are now shown to facilitate spreading of prions between neuronal cells, as well as their propagation from dentritic cells to primary neurons.

First Paragraph - | Full Text - Prions hijack tunnelling nanotubes for intercellular spread | PDF (2,572 KB) - Prions hijack tunnelling nanotubes for intercellular spread | Supplementary information

See also: News and Views by Gerdes

SOAR and the polybasic STIM1 domains gate and regulate Orai channels - pp337 - 343

Joseph P. Yuan, Weizhong Zeng, Michael R. Dorwart, Young-Jin Choi, Paul F. Worley & Shmuel Muallem

doi:10.1038/ncb1842

The molecular determinants of gating and regulation of the calcium channel Orai1 by the ER Ca²⁺ sensor STIM1 during store-operated calcium entry are now defined.

First Paragraph - | Full Text - SOAR and the polybasic STIM1 domains gate and regulate Orai channels | PDF (3,323 KB) - SOAR and the polybasic STIM1 domains gate and regulate Orai channels | Supplementary information

The yeast global transcriptional co-repressor protein Cyc8 can propagate as a prion - pp344 - 349

Basant K. Patel, Jackie Gavin-Smyth & Susan W. Liebman

doi:10.1038/ncb1843

The transcriptional activator SWI was recently shown to propagate as a prion in yeast. Cyc8, a co-repressor that regulates a similar set of genes as SWI, also propagates as a prion, suggesting a link between chromatin remodelling and cytoplasmic inheritance of prion traits.

First Paragraph - | Full Text - The yeast global transcriptional co-repressor protein Cyc8 can propagate as a prion | PDF (1,144 KB) - The yeast global transcriptional co-repressor protein Cyc8 can propagate as a prion | Supplementary information

See also: News and Views by Tuite & Cox

Nuclear transport factor directs localization of protein synthesis during mitosis - pp350 - 356

Geert van den Bogaart, Anne C. Meinema, Victor Krasnikov, Liesbeth M. Veenhoff & Bert Poolman

doi:10.1038/ncb1844

The intracellular localization of the karyopherin KAP104 determines where dissociation of the mRNA binding proteins Nab2 and Nab4 from translation competent mRNAs takes place, thus controlling local protein synthesis.

First Paragraph - | Full Text - Nuclear transport factor directs localization of protein synthesis during mitosis | PDF (2,525 KB) - Nuclear transport factor directs localization of protein synthesis during mitosis | Supplementary information

See also: News and Views by Goldfarb

The heterochromatin protein Swi6/HP1 activates replication origins at the pericentromeric region and silent mating-type locus - pp357 - 362

Makoto T. Hayashi, Tatsuro S. Takahashi, Takuro Nakagawa, Jun-ichi Nakayama & Hisao Masukata

doi:10.1038/ncb1845

The replication of heterochromatic chromosome regions is temporally regulated. The yeast heterochromatin protein Swi6 (mammalian HP1) activates replication origins by recruiting the kinase Dfp1, which facilitates loading of replication factor Sld3 on early replicating heterochromatin.

First Paragraph - | Full Text - The heterochromatin protein Swi6/HP1 activates replication origins at the pericentromeric region and silent mating-type locus | PDF (4,075 KB) - The heterochromatin protein Swi6/HP1 activates replication origins at the pericentromeric region and silent mating-type locus | Supplementary information