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:

• Stem cells: Self-help in the niche | PDF (144 KB)
  - Nat Rev Mol Cell Biol 13(2):61 (2012)
  Stem cells and progenitor cells reside in a microenvironment, or niche, that regulates their activity. Mondal et al.Drosophila melanogaster, differentiating blood cells themselves produce signals that, together with cues from the surrounding niche, contribute to the maintenance of their haematopoietic progenitors.
• Post-translational modification: Inactivating PTP1B upon ER stress | PDF (161 KB)
  - Nat Rev Mol Cell Biol 13(2):62 (2012)
  The gaseous signalling molecule hydrogen sulphide (H2S) regulates a range of cellular processes by causing the sulphydration of Cys residues (that is, the formation of Cys–SSH groups) in target proteins. Protein Tyr phosphatases (PTPs) use an essential Cys (Cys215) in their catalytic site to dephosphorylate Tyr residues in target proteins.
• Stem cells: Making fat | PDF (247 KB)
  - Nat Rev Mol Cell Biol 13(2):62 (2012)
  Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells have the potential to produce patient-specific in vitro cell models to study disease. However, converting these cells into relevant adult cell types remains a challenge.
• Monkeys show the way | PDF (82 KB)
  - Nat Rev Mol Cell Biol 13(2):62 (2012)
  The first chimeric non-human primates have been generated in a laboratory in Oregon, USA. The work, which was reported in Cell, gave rise to three rhesus monkeys: Chimero and the twins Roku and Hex. The generation of chimeric mice has been an important tool for understanding normal embryonic development and disease and has indicated that embryonic stem (ES) cells are pluripotent and can give rise to all cell types. By carrying out research in monkeys, the group of Shoukhrat Mitalipov, at the Oregon National Primate Research Center, aimed to determine whether this also applies to primates, including humans, and whether human stem cells will have "potential, especially for regenerative medicine, where they can develop into mature and functional tissues and organs." (Reuters, 5 Jan 2012.) Interestingly, they observed that injection of cultured primate ES cells into blastocysts did not lead to the generation of chimaeras, unlike what is seen with mouse ES cells. Instead, chimaeras could be generated by aggregating cells from multiple four-cell embryos without prior culture. As commented by Mitalipov, "the cells never fuse, but they stay together and work together to form tissues and organs." (Scientific American, 6 Jan 2012.) The work has important implications; as commented by Robin Lovell-Badge, from the National Institute for Medical Research in Mill Hill, UK, "assumptions about the way human embryos develop have always been based on the mouse." (bbc.co.uk, 5 Jan 2012.) A related commentary in Cell postulates that this discrepancy could be due to differences in developmental status — primate ES cells may be more developmentally advanced than mouse ones. So, it seems that further work is needed in primates to better understand the properties of human ES cells.
• Ubiquitylation: DUBs' key to selectivity | PDF (124 KB)
  - Nat Rev Mol Cell Biol 13(2):64 (2012)
  Some deubiquitylating enzymes (DUBs) are specific for distinct ubiquitin linkages, but the molecular basis for this is largely unknown. TRABID, a DUB belonging to the ovarian tumour (OTU) family, has previously been shown to hydrolyze atypical Lys29-linked ubiquitin chains more efficiently than other linkages.
• Cell cycle: AMPK moonlights in mitosis | PDF (224 KB)
  - Nat Rev Mol Cell Biol 13(2):64 (2012)
  AMP-activated protein kinase (AMPK) is well known for its ability to regulate cell metabolism, but emerging evidence suggests that it functions in additional cellular processes. Banko et al.
• RNA decay: Remember your driver | PDF (140 KB)
  - Nat Rev Mol Cell Biol 13(2):65 (2012)
  The stability of mRNA is often assumed to be dictated by a transcript's sequence features. Two new studies highlight that mRNA stability can be influenced by a memory of the promoter from which expression of the transcript was driven.
• Post-translational modification: A monoubiquitylation pore anchor | PDF (181 KB)
  - Nat Rev Mol Cell Biol 13(2):66 (2012)
  The nuclear pore complex (NPC), which consists of ~30 nucleoporins (NUPs), has additional roles beyond its core function in nuclear transport. Post-translational modification of NUPs by ubiquitylation and phosphorylation can affect NUP turnover and pore disassembly, respectively, and may offer the opportunity for fine-tuning NUP functions beyond transport.
• How a paper on RAC set the standard | PDF (110 KB)
  - Nat Rev Mol Cell Biol 13(2):66 (2012)
  Modern cell biology is full of well-analysed signalling pathways that control every facet of a cell's life. To a student or postdoctoral researcher, it probably seems as if it has always been so, but it is a recent phenomenon.
• Cytoskeleton: Making multiple cilia | PDF (85 KB)
  - Nat Rev Mol Cell Biol 13(2):63 (2012)
  How centriole assembly and outgrowth of motile cilia are driven during multiciliate cell (MCC) differentiation is unclear, although Notch signalling is known to inhibit MCC formation in epithelia. Stubbs et al.Xenopus laevis skin, so they assessed its ability to promote MCC differentiation.
• 
  - Nat Rev Mol Cell Biol 13(2):63 (2012)
  
• 
  - Nat Rev Mol Cell Biol 13(2):63 (2012)
  
• Illuminating the functional and structural repertoire of human TBC/RABGAPs
  - Nat Rev Mol Cell Biol 13(2):67 (2012)
  The Tre2–Bub2–Cdc16 (TBC) domain-containing RAB-specific GTPase-activating proteins (TBC/RABGAPs) are characterized by the presence of highly conserved TBC domains and act as negative regulators of RABs. The importance of TBC/RABGAPs in the regulation of specific intracellular trafficking routes is now emerging, as is their role in different diseases. Importantly, TBC/RABGAPs act as key regulatory nodes, integrating signalling between RABs and other small GTPases and ensuring the appropriate retrieval, transport and delivery of different intracellular vesicles.
• Dynamin, a membrane-remodelling GTPase
  - Nat Rev Mol Cell Biol 13(2):75 (2012)
  Dynamin, the founding member of a family of dynamin-like proteins (DLPs) implicated in membrane remodelling, has a critical role in endocytic membrane fission events. The use of complementary approaches, including live-cell imaging, cell-free studies, X-ray crystallography and genetic studies in mice, has greatly advanced our understanding of the mechanisms by which dynamin acts, its essential roles in cell physiology and the specific function of different dynamin isoforms. In addition, several connections between dynamin and human disease have also emerged, highlighting specific contributions of this GTPase to the physiology of different tissues.
• The unfolded protein response: controlling cell fate decisions under ER stress and beyond
  - Nat Rev Mol Cell Biol 13(2):89 (2012)
  Protein-folding stress at the endoplasmic reticulum (ER) is a salient feature of specialized secretory cells and is also involved in the pathogenesis of many human diseases. ER stress is buffered by the activation of the unfolded protein response (UPR), a homeostatic signalling network that orchestrates the recovery of ER function, and failure to adapt to ER stress results in apoptosis. Progress in the field has provided insight into the regulatory mechanisms and signalling crosstalk of the three branches of the UPR, which are initiated by the stress sensors protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1α (IRE1α) and activating transcription factor 6 (ATF6). In addition, novel physiological outcomes of the UPR that are not directly related to protein-folding stress, such as innate immunity, metabolism and cell differentiation, have been revealed.
• A family business: stem cell progeny join the niche to regulate homeostasis
  - Nat Rev Mol Cell Biol 13(2):103 (2012)
  Stem cell niches, the discrete microenvironments in which the stem cells reside, play a dominant part in regulating stem cell activity and behaviours. Recent studies suggest that committed stem cell progeny become indispensable components of the niche in a wide range of stem cell systems. These unexpected niche inhabitants provide versatile feedback signals to their stem cell parents. Together with other heterologous cell types that constitute the niche, they contribute to the dynamics of the microenvironment. As progeny are often located in close proximity to stem cell niches, similar feedback regulations may be the underlying principles shared by different stem cell systems.
• Understanding the language of Lys36 methylation at histone H3
  - Nat Rev Mol Cell Biol 13(2):115 (2012)
  Histone side chains are post-translationally modified at multiple sites, including at Lys36 on histone H3 (H3K36). Several enzymes from yeast and humans, including the methyltransferases SET domain-containing 2 (Set2) and nuclear receptor SET domain-containing 1 (NSD1), respectively, alter the methylation status of H3K36, and significant progress has been made in understanding how they affect chromatin structure and function. Although H3K36 methylation is most commonly associated with the transcription of active euchromatin, it has also been implicated in diverse processes, including alternative splicing, dosage compensation and transcriptional repression, as well as DNA repair and recombination. Disrupted placement of methylated H3K36 within the chromatin landscape can lead to a range of human diseases, underscoring the importance of this modification.
• Satellite cells, the engines of muscle repair
  - Nat Rev Mol Cell Biol 13(2):127 (2012)
  Satellite cells are a heterogeneous population of stem and progenitor cells that are required for the growth, maintenance and regeneration of skeletal muscle. The transcription factors paired-box 3 (PAX3) and PAX7 have essential and overlapping roles in myogenesis. PAX3 acts to specify embryonic muscle precursors, whereas PAX7 enforces the satellite cell myogenic programme while maintaining the undifferentiated state. Recent experiments have suggested that PAX7 is dispensable in adult satellite cells. However, these findings are controversial, and the issue remains unresolved.