Hot off the presses! Feb 01 Nat Rev Mol Cell Biol

The Feb 01 issue of the Nat Rev Mol Cell Biol is now up on Pubget (About Nat Rev Mol Cell Biol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

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  - Nat Rev Mol Cell Biol 12(2):71 (2011)
  
• Membrane trafficking: A GSK3 lockdown | PDF (322 KB)
  - Nat Rev Mol Cell Biol 12(2):72 (2011)
  A vital step in the WNT signalling pathway is inhibition of glycogen synthase kinase 3 (GSK3), but how this takes place had remained elusive. It turns out that activation of WNT signalling drives GSK3 into multivesicular bodies (MVBs), effectively locking it away from cytosolic substrates.
• Cytoskeleton: N-WASP 'muscles in' on actin nucleation | PDF (184 KB)
  - Nat Rev Mol Cell Biol 12(2):73 (2011)
  Muscle maturation and hypertrophy require the activation of protein synthesis and myofibrillogenesis. Takano et al.
• 'Tit-for-tat' in cell biology | PDF (142 KB)
  - Nat Rev Mol Cell Biol 12(2):73 (2011)
  Although my colleagues (and, hopefully, readers) value the importance of evolutionary theory in biology, many of us fail to incorporate it into our research. Therefore, I am going to tell you about a paper that influenced me long ago.
• Cell migration: MTORC2 brings up the rear | PDF (191 KB)
  - Nat Rev Mol Cell Biol 12(2):74 (2011)
  Target of rapamycin complex 2 (TORC2) is known to have a role in the chemotaxis of Dictyostelium discoideum, and its mammalian counterpart, mTORC2, regulates cytoskeletal reorganization in some cell lines. Parent and colleagues now find that mTORC2 also has a role in neutrophil chemotaxis through control of cell-rear retraction.
• Cell migration: Keeping together | PDF (207 KB)
  - Nat Rev Mol Cell Biol 12(2):74 (2011)
  Collective cell movement — needed for normal development but also associated with the invasion of cancer cells — requires organization and coordination. An actomyosin force around the edge of a migrating cell cluster facilitates coordinated movement, but contractility at cell–cell contacts inside the cluster must be reduced to maintain group cohesion.
• Cell signalling: Targeting kinases | PDF (129 KB)
  - Nat Rev Mol Cell Biol 12(2):75 (2011)
  The spatial regulation of signalling pathways is partly controlled by protein domains that mediate intermolecular interactions. Human MARK (MAP/microtubule affinity-regulating kinases) and PAR1 (partitioning-defective 1) Ser/Thr kinases harbour a kinase-associated 1 (KA1) domain, which has no assigned function.
• Cell signalling: Weighing up TGFβ signals | PDF (145 KB)
  - Nat Rev Mol Cell Biol 12(2):76 (2011)
  Signalling through the Hippo pathway allows sensing of local cell density and subsequent control of cell growth, proliferation and apoptosis. The transcriptional regulators TAZ and YAP are key components in this response, and Varelas et al.
• Development: A new move for PRMT5 | PDF (178 KB)
  - Nat Rev Mol Cell Biol 12(2):76 (2011)
  To establish and maintain pluripotency, cells must tightly regulate gene expression. Protein Arg N-methyltransferase 5 (PRMT5) is crucial for the development of primordial germ cells, and there have been suggestions that it might also be involved in embryonic stem (ES) cell pluripotency.
• Gene expression | Autophagy | Stem cells | PDF (127 KB)
  - Nat Rev Mol Cell Biol 12(2):76 (2011)
  Selective silencing of mutated mRNAs in DM1 by using modified hU7-snRNAs François, V.et al. Nature Struct. Mol. Biol. 18, 85–87 (2011)
• Autophagy: Myosin II moves in on autophagosomes | PDF (135 KB)
  - Nat Rev Mol Cell Biol 12(2):77 (2011)
  During starvation-induced autophagy, cytosol or organelles are engulfed by autophagosomes, the contents of which are degraded by lysosomes and released as nutrients. The kinase Autophagy-related 1 (ATG1) is important for autophagosome formation, but its exact role was unclear.
• Dedifferentiation, transdifferentiation and reprogramming: three routes to regeneration
  - Nat Rev Mol Cell Biol 12(2):79 (2011)
  The ultimate goal of regenerative medicine is to replace lost or damaged cells. This can potentially be accomplished using the processes of dedifferentiation, transdifferentiation or reprogramming. Recent advances have shown that the addition of a group of genes can not only restore pluripotency in a fully differentiated cell state (reprogramming) but can also induce the cell to proliferate (dedifferentiation) or even switch to another cell type (transdifferentiation). Current research aims to understand how these processes work and to eventually harness them for use in regenerative medicine.
• The MRE11 complex: starting from the ends
  - Nat Rev Mol Cell Biol 12(2):90 (2011)
  The maintenance of genome stability depends on the DNA damage response (DDR), which is a functional network comprising signal transduction, cell cycle regulation and DNA repair. The metabolism of DNA double-strand breaks governed by the DDR is important for preventing genomic alterations and sporadic cancers, and hereditary defects in this response cause debilitating human pathologies, including developmental defects and cancer. The MRE11 complex, composed of the meiotic recombination 11 (MRE11), RAD50 and Nijmegen breakage syndrome 1 (NBS1; also known as nibrin) proteins is central to the DDR, and recent insights into its structure and function have been gained from in vitro structural analysis and studies of animal models in which the DDR response is deficient.
• Feedback regulation of EGFR signalling: decision making by early and delayed loops
  - Nat Rev Mol Cell Biol 12(2):104 (2011)
  Human-made information relay systems invariably incorporate central regulatory components, which are mirrored in biological systems by dense feedback and feedforward loops. This type of system control is exemplified by positive and negative feedback loops (for example, receptor endocytosis and dephosphorylation) that enable growth factors and receptor Tyr kinases of the epidermal growth factor receptor (EGFR)/ERBB family to regulate cellular function. Recent studies show that the collection of feedback regulatory loops can perform computational tasks — such as decoding ligand specificity, transforming graded input signals into a digital output and regulating response kinetics. Aberrant signal processing and feedback regulation can lead to defects associated with pathologies such as cancer.
• Origins of regulated cell-to-cell variability
  - Nat Rev Mol Cell Biol 12(2):119 (2011)
  Single-cell measurements and lineage-tracing experiments are revealing that phenotypic cell-to-cell variability is often the result of deterministic processes, despite the existence of intrinsic noise in molecular networks. In most cases, this determinism represents largely uncharacterized molecular regulatory mechanisms, which places the study of cell-to-cell variability in the realm of molecular cell biology. Further research in the field will be important to advance quantitative cell biology because it will provide new insights into the mechanisms by which cells coordinate their intracellular activities in the spatiotemporal context of the multicellular environment.
• The elusive nature and function of mesenchymal stem cells
  - Nat Rev Mol Cell Biol 12(2):126 (2011)
  Mesenchymal stem cells (MSCs) are a diverse subset of multipotent precursors present in the stromal fraction of many adult tissues and have drawn intense interest from translational and basic investigators. MSCs have been operationally defined by their ability to differentiate into osteoblasts, adipocytes and chondrocytes after in vitro expansion. Nevertheless, their identity in vivo, heterogeneity, anatomical localization and functional roles in adult tissue homeostasis have remained enigmatic and are only just starting to be uncovered.