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- A new issue of Molecular Biology of the Cell is available online:
- 15 March 2010; Vol. 21, No. 6
- The below Table of Contents is available online at: http://www.molbiolcell.org/content/vol21/issue6/?etoc
Meeting Review
- Jennifer A. Zallen and Alpha S. Yap
Cell Cycle
Mutations in Caenorhabditis elegans him-19 Show Meiotic Defects That Worsen with Age A Highlights from MBoC Selection - Lois Tang, Thomas Machacek, Yasmine M. Mamnun, Alexandra Penkner, Jiradet Gloggnitzer, Christina Wegrostek, Robert Konrat, Michael F. Jantsch, Josef Loidl, and Verena Jantsch
Faithful meiotic chromosome segregation requires pairing, synapsis and recombination of homologous chromosomes. In mammals, chromosomal non-disjunction increases with age. A mutation in Caenorhabditis elegans him-19 mimics these age-dependent chromosome segregation defects and might therefore further our understanding of this phenomenon.
- Jorge Z. Torres, Kenneth H. Ban, and Peter K. Jackson
The anaphase-promoting complex/cyclosome (APC/C) is phosphorylated in a cell cycle dependent manner. We discovered that a specific form of PPP2 is necessary for APC/C dephosphorylation in mitosis and that this dephosphorylation event regulates the association of the APC/C with mitotic spindle poles.
Emi2 Inhibition of the Anaphase-promoting Complex/Cyclosome Absolutely Requires Emi2 Binding via the C-Terminal RL Tail A Highlights from MBoC Selection - Munemichi Ohe, Yoshiko Kawamura, Hiroyuki Ueno, Daigo Inoue, Yoshinori Kanemori, Chiharu Senoo, Michitaka Isoda, Nobushige Nakajo, and Noriyuki Sagata
Both the D-box and the zinc-binding region (ZBR) of Emi2 are implicated in APC/C inhibition. This article shows that Emi2 binds the APC/C via the C-terminal tail, termed here the RL tail. The RL tail apparently promotes the inhibitory interactions of the D-box and the ZBR with the APC/C. The RL tail thus serves as a docking site for the APC/C.
Requirements and Reasons for Effective Inhibition of the Anaphase Promoting Complex Activator Cdh1 A Highlights from MBoC Selection - Jonathan A. Robbins and Frederick R. Cross
Inhibitory phosphorylation of Cdh1 by CDK and Polo kinase has been proposed to inactivate APC-Cdh1. Through an exact gene replacement approach, we find CDK, but not Polo, phosphorylation of Cdh1 to be a critical regulatory mechanism. APC-Cdh1 inhibits multiple aspects of spindle morphogenesis, and its activity is modulated by endogenous ACM1.
Rad17 Plays a Central Role in Establishment of the Interaction between TopBP1 and the Rad9-Hus1-Rad1 Complex at Stalled Replication Forks A Highlights from MBoC Selection - Joon Lee and William G. Dunphy
This work provides novel mechanistic insights into how TopBP1 and the Rad9-Hus1-Rad1 (9-1-1) complex dock with one another at stalled replication forks. This step is necessary for the ATR-dependent activation of Chk1 during checkpoint responses.
Cell Motility
- Arjan Kortholt, Parvin Bolourani, Holger Rehmann, Ineke Keizer-Gunnink, Gerald Weeks, Alfred Wittinghofer, and Peter J.M. Van Haastert
GbpD, a guanine exchange factor specific for Rap1, has been implicated in adhesion, cell polarity, and chemotaxis of Dictyostelium cells. Here it is shown that activated Rap1 directly binds to PI3K. The activation of PI3K by Rap1 and RasG regulates basal and chemoattractant-stimulated PIP3 levels and pseudopod formation.
- Salma Taboubi, Françoise Garrouste, Fabrice Parat, Gilbert Pommier, Emilie Faure, Sylvie Monferran, Hervé Kovacic, and Maxime Lehmann
After skin wound, released growth factors and extracellular nucleotides regulate the different phases of healing, including re-epithelialization. Here, we show that, in keratinocytes, purinergic P2Y2 receptors inhibit the motogenic IGF-I/PI3K pathway. Therefore, extracellular nucleotides may play key roles during skin remodelling after wound.
Membrane Trafficking
- Nobumichi Furuta, Naonobu Fujita, Takeshi Noda, Tamotsu Yoshimori, and Atsuo Amano
Autophagy (xenophagy) degrades intracellular bacteria. The cargoes are degraded after the fusion of xenophagosomes with lysosomes. However, the molecular mechanism underlying the fusion remains unclear. Here we show that combinational SNARE proteins VAMP8 and Vti1b mediate fusion of antimicrobial and canonical autophagosomes with lysosomes.
- Ganesh Varma Pusapati, Denis Krndija, Milena Armacki, Götz von Wichert, Julia von Blume, Vivek Malhotra, Guido Adler, and Thomas Seufferlein
The present study provides the first link between the "classical" machinery regulating protein transport at the Golgi compartment, namely ARF proteins and PKDs, and demonstrates that the direct interaction of both is crucial for efficient protein transport from the TGN to the plasma membrane.
- Daniel P. Nickerson, Matthew West, Ryan Henry, and Greg Odorizzi
Disassembly of ESCRT-III requires Vps4 ATPase activity under the control of regulatory proteins. Described here are distinct spatiotemporal functions for Vps4 regulators, with Did2 playing a unique role in regulating MVB lumenal vesicle size and Vtal-Vps60 promoting efficient membrane scission and delivery of vesicles into the endosome lumen.
- Marvin Bentley, Deborah C. Nycz, Ashwini Joglekar, Ismene Fertschai, Roland Malli, Wolfgang F. Graier, and Jesse C. Hay
This study establishes a role for luminal Ca2+ in ER/Golgi transport organelles and elucidates an effector mechanism involving the EF-hand protein ALG-2 and regulation of COPII coat retention.
- Teresa M. Buck, Alexander R. Kolb, Cary R. Boyd, Thomas R. Kleyman, and Jeffrey L. Brodsky
This study describes new yeast expression systems for each subunit of the heterotrimeric epithelial sodium channel (ENaC). We found that a significant amount of each subunit resides in the ER and is destroyed via ERAD. We also found that the chaperone requirements for ENaC subunit degradation were unlike any other ERAD substrate examined.
- Anna Shestakova, Abraham Hanono, Stacey Drosner, Matt Curtiss, Brian A. Davies, David J. Katzmann, and Markus Babst
A complex network of interactions mediates the recruitment of Vps4 to ESCRT-III and its subsequent assembly, two key steps in the ESCRT-dependent vesicle formation at the endosome. A model is presented depicting the order of events that lead to active, ESCRT-III–associated Vps4.
Nuclear Functions
- Laura C. Titus, T. Renee Dawson, Deborah J. Rexer, Kathryn J. Ryan, and Susan R. Wente
Genome-wide screening approaches were employed to identify factors required for nuclear pore complex structure and distribution in Saccharomyces cerevisiae. Roles were found for multiple components of the RSC complex, revealing a functional connection between proper chromatin remodeling and nuclear envelope/nuclear pore complex structure.
Signaling
- Sayaka Yoshiki, Rie Matsunaga-Udagawa, Kazuhiro Aoki, Yuji Kamioka, Etsuko Kiyokawa, and Michiyuki Matsuda
Activation of Raf1 at the plasma membrane requires not only Ras activation but also an increase in Ca2+ concentration or inhibition of calmodulin. The Ca2+-dependent activation of Raf1 is abrogated by knockdown of Shoc2. We show that the Shoc2 scaffold protein modulates Ras-dependent Raf1 activation in a Ca2+- and calmodulin-dependent manner.
Compartmentalized Cyclic Adenosine 3',5'-Monophosphate at the Plasma Membrane Clusters PDE3A and Cystic Fibrosis Transmembrane Conductance Regulator into Microdomains A Highlights from MBoC Selection - Himabindu Penmatsa, Weiqiang Zhang, Sunitha Yarlagadda, Chunying Li, Veronica G. Conoley, Junming Yue, Suleiman W. Bahouth, Randal K. Buddington, Guangping Zhang, Deborah J. Nelson, Monal D. Sonecha, Vincent Manganiello, Jeffrey J. Wine, and Anjaparavanda P. Naren
PDE3A functionally and physically interacts with CFTR. Inhibition of PDE3A generates compartmentalized cAMP, which further clusters PDE3A and CFTR into microdomains at the plasma membrane of epithelial cells and potentiates CFTR channel function. Our findings provide insights into the important role of PDE3A in compartmentalized cAMP signaling.
- Francesca Cencetti, Caterina Bernacchioni, Paola Nincheri, Chiara Donati, and Paola Bruni
Transforming growth factor-β1 induces Smad-dependent transdifferentiation of myoblasts into myofibroblasts via up-regulation of sphingosine kinase-1/S1P3 axis with a mechanism involving Rho/Rho kinase activation.
- Celia Quevedo, Vincent Sauzeau, Mauricio Menacho-Márquez, Antonio Castro-Castro, and Xosé R. Bustelo
Vav proteins are phosphorylation-dependent Rho/Rac exchange factors that have usually been associated with immune- and cardiovascular-related functions. In this paper, Quevedo et al. demonstrate that Vav3 plays important, although transient, pleiotropic roles during the postnatal development of the cerebellum.
- Amrik Singh, Min Ye, Octavian Bucur, Shudong Zhu, Maria Tanya Santos, Isaac Rabinovitz, Wenyi Wei, Daming Gao, William C. Hahn, and Roya Khosravi-Far
This article describes a functional interaction between PP2A and FOXO3a in which PP2A promotes rapid dephosphorylation of FOXO3a at its conserved AKT phosphorylation sites, leading to FOXO3a dissociation from 14-3-3, nuclear translocation, and transcriptional activation in response to inhibition of PI3K signaling.
Meeting Review
- Jennifer A. Zallen and Alpha S. Yap
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