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

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Latest Articles Include:

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  - Nat Rev Mol Cell Biol 12(9):543 (2011)
  
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  - Nat Rev Mol Cell Biol 12(9):545 (2011)
  
• Development: Staying big-brained
  - Nat Rev Mol Cell Biol 12(9):546 (2011)
  During animal development, nutrient deprivation can lead to the growth of some 'privileged' organs, such as the central nervous system (CNS), at the expense of others. Gould and colleagues investigated this organ 'sparing' mechanism in Drosophila melanogaster and identified a signalling pathway involving anaplastic lymphoma kinase (ALK) that protects the CNS during starvation.
• Metabolism: Metabolic regulation by ERK
  - Nat Rev Mol Cell Biol 12(9):546 (2011)
  Normal cells require attachment to the extracellular matrix (ECM) to survive, and ECM detachment causes metabolic impairments (such as reduced ATP levels), largely through a reduction in nutrient uptake owing to decreased phosphoinositide 3-kinase signalling. Grassian et al.
• Cell death: A new platform for death
  - Nat Rev Mol Cell Biol 12(9):547 (2011)
  Recent studies have highlighted the intricate relationship between apoptotic and necroptotic cell death, although the molecular details of this were incomplete. Two groups now identify a ~2 MDa signalling platform, which they term the 'Ripoptosome', that activates both cell death pathways.
• Cytoskeleton: N-WASP supports junctional integrity
  - Nat Rev Mol Cell Biol 12(9):548 (2011)
  Neural Wiskott–Aldrich syndrome protein (N-WASP) is a cytoskeletal regulator that stimulates actin nucleation through the actin-related protein 2/3 (ARP2/3) complex. Kovacs et al.
• Replication: Checkpoint tension relief
  - Nat Rev Mol Cell Biol 12(9):548 (2011)
  Transcription and DNA replication are coordinated, and replication forks are known to pause when they encounter a transcribing gene. Foiani and colleagues propose that the replication checkpoint may respond to such collisions by triggering the release of transcribed genes from the nuclear pore complex (NPC), thereby relieving topological tension on the DNA.
• Membrane trafficking | Ubiquitylation | Small RNAs
  - Nat Rev Mol Cell Biol 12(9):548 (2011)
  The COG complex interacts directly with syntaxin 6 and positively regulates endosome-to-TGN retrograde transport Laufman, O., Hong, W. & Lev, S.J. Cell Biol. 194, 459–472 (2011)
• Development | Epigenetics | Development
  - Nat Rev Mol Cell Biol 12(9):549 (2011)
  Development Notch and Ras promote sequential steps of excretory tube development in C. elegans Abdus-Saboor, I. Development138, 3545–3555(2011)Article The excretory organ in Caenorhabditis elegans is made up of three stacked unicellular tubes — an excretory canal cell, a duct and a G1 pore, the second two of which arise from one of two equivalent progenitor cells. Abdus-Saboor et al. now show that LET-60 (RAS in mammals) promotes duct over G1 pore identity, as well as the stacking of the duct and G1 pore next to the canal cell, through the canonical LIN-3–LET-60–mitogen-activated protein kinase 1 pathway. The canal cell, which they found to express LIN-3 (epidermal growth factor in mammals), is required for duct and G1 pore stacking, as its removal (by inhibition of Notch signalling) disrupted this. So, Notch signalling promotes the formation of LIN-3-expressing canal cells, and LIN-3 activates LET-60 signalling in one progenitor cell to promote duct formation. Epigenetics Jarid2 regulates mouse epidermal stem cell activation and differentiation Mejetta, S. et al.EMBO J.2 Aug 2011 (doi:10.1038/emboj.2011.265) * Article In embryonic stem cells, JARID2 (jumonji and ARID domain-containing 2) is required for the recruitment of polycomb repressive complex 2 (PRC2), which catalyses histone H3 Lys27 trimethylation (H3K27me3); however, the role of JARID2 in late development and adult tissues was not well understood. Mejetta et al. conditionally deleted JARID2 in mouse epidermis and found that it is involved in maintaining robust proliferation of hair follicles during the postnatal anagen (growth) phase. JARID2 was dispensable for embryonic epidermal development but was important postnatally, as loss of JARID2 reduced proliferation and enhanced differentiation of postnatal epidermal progenitor cells. Consistent with JARID2's function in recruiting PRC2, there was a mild reduction in global H3K27me3 and reduced H3K27me3 at known PRC2 target genes in JARID2-knockout neonatal epidermis. The authors propose that JARID2 functions to maintain normal epidermal homeostasis and is required for efficient pos! tnatal activation of hair follicle stem cells. Development On the growth and form of the gut Savin, T. et al.Nature476, 57–62(2011) * Article Savin et al. studied the looping morphogenesis of the gut in vertebrates as an example of the role of mechanical forces in organogenesis. The gut starts as a linear tube and forms a looped pattern as it develops in the body cavity. By carrying out surgical experiments, the authors showed that loop formation results from tissues growing at different rates — there is uniform differential growth between the gut tube and the anchoring dorsal mesentery (a structure of mesodermal origin that is important for gut development and the normal function of the adult digestive system). The authors then simulated the formation of the loop pattern using a simple physical model based on a rubber tube and a thin latex tube. This system was used to develop a computational model that predicts the number, size and shape of intestinal loops based solely on mechanical properties of tissues: geometry, elasticity and relative growth. This should help to understand how biophysical and biochemical ! events drive tissue development.
• Protein stability: BAG6 'mops up' mislocalized proteins
  - Nat Rev Mol Cell Biol 12(9):550 (2011)
  Membrane proteins that are not correctly targeted are instead released into the cytosol. Such mislocalized proteins need to be removed to avoid, for example, the accumulation of protein aggregates.
• Cell signalling: JH2 is active!
  - Nat Rev Mol Cell Biol 12(9):550 (2011)
  Janus kinase 2 (JAK2) is a cytoplasmic Tyr kinase that has a crucial function in mediating the signalling of haematopoietic hormones and cytokines. JAK2 is regulated both positively and negatively by phosphorylation.
• Molecular control of endothelial cell behaviour during blood vessel morphogenesis
  - Nat Rev Mol Cell Biol 12(9):551 (2011)
  The vertebrate vasculature forms an extensive branched network of blood vessels that supplies tissues with nutrients and oxygen. During vascular development, coordinated control of endothelial cell behaviour at the levels of cell migration, proliferation, polarity, differentiation and cell–cell communication is critical for functional blood vessel morphogenesis. Recent data uncover elaborate transcriptional, post-transcriptional and post-translational mechanisms that fine-tune key signalling pathways (such as the vascular endothelial growth factor and Notch pathways) to control endothelial cell behaviour during blood vessel sprouting (angiogenesis). These emerging frameworks controlling angiogenesis provide unique insights into fundamental biological processes common to other systems, such as tissue branching morphogenesis, mechanotransduction and tubulogenesis.
• Calcium: Mitochondria channel calcium
  - Nat Rev Mol Cell Biol 12(9):550 (2011)
  It has come to our attention that Baughman et al. reported similar findings in parallel to those discussed in this Research Highlight, identifying the core component of the elusive mitochondrial calcium uniporter (MCU), which they termed MCU, through genomic, physiological, biochemical and pharmacological approaches. We apologize to the authors of this paper for the omission.
• The predator becomes the prey: regulating the ubiquitin system by ubiquitylation and degradation
  - Nat Rev Mol Cell Biol 12(9):605 (2011)
  Ubiquitylation (also known as ubiquitination) regulates essentially all of the intracellular processes in eukaryotes through highly specific modification of numerous cellular proteins, which is often tightly regulated in a spatial and temporal manner. Although most often associated with proteasomal degradation, ubiquitylation frequently serves non-proteolytic functions. In light of its central roles in cellular regulation, it has not been surprising to find that many of the components of the ubiquitin system itself are regulated by ubiquitylation. This observation has broad implications for pathophysiology.