• Article |

    Polycystic kidney disease family proteins form heteromeric complexes with transient receptor potential channel subunits of the TRPP subfamily. Yu and colleagues find that the polycystic kidney disease protein, PKD1L3, is an ion channel pore-forming subunit in the acid-sensing PKD1L3/TRPP3 complex.

    • Yong Yu
    • , Maximilian H. Ulbrich
    •  & Jian Yang
  • Article |

    The plasma membrane is thought to comprise a patchwork of ordered and disordered microdomains; however, direct evidence for this in intact cells remains elusive. Using unmixing of fluorescence lifetime decays, Owen et al. show that ordered domains occupy a majority of the plasma membrane surface in living cells.

    • Dylan M. Owen
    • , David J. Williamson
    •  & Katharina Gaus
  • Article |

    Enzymes are traditionally viewed as being highly specific for their substrates. Tokuriki et al.follow the accumulation of mutations during the laboratory evolution of a phosphotriesterase into an arylesterase, and postulate that many naturally occurring enzymes may not be optimal for their substrates.

    • Nobuhiko Tokuriki
    • , Colin J. Jackson
    •  & Dan S. Tawfik
  • Article |

    Multifunctional S100 proteins are upregulated in brain injury, but their role in neurodegeneration is not clear. Dmytriyeva and colleagues study in vivomodels of brain trauma and find that the S100A4 protein and its peptide mimetics protect neurons via the interleukin-10 receptor and the Janus kinase (JAK)/STAT pathway.

    • Oksana Dmytriyeva
    • , Stanislava Pankratova
    •  & Darya Kiryushko
  • Article |

    The temporal opening and closing of cell–cell junctions at the blood–testis barrier allows the passage of immature germ cells during spermatogenesis. Su and colleagues identify a peptide fragment of the laminin-γ3 chain that disrupts the blood–testis barrier and reversibly impairs spermatogenesis in rats.

    • Linlin Su
    • , Dolores D. Mruk
    •  & C. Yan Cheng
  • Article |

    Sequence-specific DNA endonucleases have found numerous applications in biology, but similar manipulations of RNA have been limited by the lack of suitable enzymes. These authors combine a cleavage domain with a designable binding domain and demonstrate the resulting RNA endonuclease's utilityin vitroand in cells.

    • Rajarshi Choudhury
    • , Yihsuan S. Tsai
    •  & Zefeng Wang
  • Article |

    Rapid synaptic transmission requires efficient recycling of synaptic vesicle membrane proteins. Sochackiet al.use live cell, electron and super-resolution microscopy to visualize exocytosis of vesicular transporters and their rapid recapture in clathrin-rich microdomains in the plasma membrane.

    • Kem A. Sochacki
    • , Ben T. Larson
    •  & Justin W. Taraska
  • Article
    | Open Access

    Prion proteins are implicated in a range of neurodegenerative diseases, which are, in part, due to a disruption of metal homeostasis. Wattet al.use selective antagonists to show that prion proteins mediate zinc uptake by interacting with GluA2-lacking, GluA1-containing AMPA receptors.

    • Nicole T. Watt
    • , David R. Taylor
    •  & Nigel M. Hooper
  • Article
    | Open Access

    The ability of oleaginous fungi to produce lipids for biofuels remains untapped, in part due to a lack of genetic information required to engineer industrial strains. Zhuet al. present the genome of R. toruloides, and identify transcriptomic and proteomic changes associated with lipid production.

    • Zhiwei Zhu
    • , Sufang Zhang
    •  & Zongbao K. Zhao
  • Article
    | Open Access

    Sodium-gated ion channels open and close in response to the flow of ions. Here, McCusker et the open structure of a sodium-gated ion channel pore from a bacterial homologue, and show, by comparison with the closed structure, that the movement of a C-terminal helix is sufficient to open the channel.

    • Emily C. McCusker
    • , Claire Bagnéris
    •  & B.A. Wallace
  • Article |

    The design of chemical photoswitches could potentially lead to the development of novel therapeutics that regulates neurotransmission. In this study, a light-sensitive modified derivative of propofol is shown to activate GABAA receptors in Xenopusoocytes, rat ganglion cells and mouse cerebellar slices.

    • Lan Yue
    • , Michal Pawlowski
    •  & David R. Pepperberg
  • Article
    | Open Access

    Cyclin B–Cdk1 is thought to be synonymous with the promoting factor that drives entry into M-phase of the cell cycle. Here, Greatwall kinase is shown to be required for the breakdown of the nuclear envelope and the assembly of the spindle on entry into M-phase, suggesting that it too is a part of the M-phase-promoting factor.

    • Masatoshi Hara
    • , Yusuke Abe
    •  & Takeo Kishimoto
  • Article |

    TGF-β signalling suppresses tumorigenesis in breast cancer cells but its effects on breast cancer initiating cells have not been reported. Using cells in culture, Brunaet al. show that TGF-β increases breast cancer initiating cell numbers in cells that have low levels of the tight junction protein claudin.

    • Alejandra Bruna
    • , Wendy Greenwood
    •  & Carlos Caldas
  • Article |

    The iron–sulphur enzyme IspH catalyses the final step of the methylerythritol phosphate isoprenoid biosynthesis pathway. Spanet al. report that IspH can hydrate acetylenes to aldehydes and ketones, in addition to its role as a 2H+/2ereductase.

    • Ingrid Span
    • , Ke Wang
    •  & Michael Groll
  • Article
    | Open Access

    Many drugs exist that target the β-adrenergic receptor, but they have different efficacies. Kofukuet al. use NMR to show that methionine 82 in the transmembrane domain undergoes conformational changes depending on whether agonists or inverse agonists are bound, explaining the differential drug efficacy.

    • Yutaka Kofuku
    • , Takumi Ueda
    •  & Ichio Shimada
  • Article |

    Methyltransferases modify cellular proteins in addition to DNA and histones. These authors identify a new family of lysine-specific methyltransferases and show that a member of this family, which is associated with tumour metastasis, methylates the ATP-dependent protein chaperone VCP/p97.

    • Stefan Kernstock
    • , Erna Davydova
    •  & Pål Ø. Falnes
  • Article |

    The mitochondrial transcription factor A (TFAM) mediates both mitochondrial transcription and DNA compaction, but how it achieves these two functions is unknown. In this study, TFAM is shown to slide along DNA and cause local melting, suggesting a mechanism for how TFAM modulates both transcription and compaction.

    • Géraldine Farge
    • , Niels Laurens
    •  & Gijs J.L. Wuite
  • Article |

    The amyloid beta peptide can aggregate into insoluble plaques, which may indicate the onset of Alzheimer's disease. In a mouse model of Alzheimer's disease, Cao and colleagues report a phenotype of altered connectivity in the olfactory neuronal circuit that precedes amyloid plaque deposition.

    • Luxiang Cao
    • , Benjamin R. Schrank
    •  & Mark W. Albers
  • Article |

    Mechanosensitive channels are required to sense cell swelling in response to osmotic shock. Nakayamaet that Msy1 and Msy2 are the fission yeast homologues of the bacterial mechanosensitive channel MscS, and are required for regulating intracellular calcium in response to cell swelling.

    • Yoshitaka Nakayama
    • , Kenjiro Yoshimura
    •  & Hidetoshi Iida
  • Article |

    Resilin is a polymeric elastic protein that is important for the flight and jumping of insects. Here, the structure-function relationships ofDrosophilaresilin are investigated, and a mechanical model is proposed to account for its elasticity.

    • Guokui Qin
    • , Xiao Hu
    •  & David L. Kaplan
  • Article |

    The bacterial channel protein MscL opens in response to mechanical forces and could be exploited for vesicular-based drug delivery. Doerneret al. show that functional MscL can be expressed in mammalian cells and facilitate the controlled cellular uptake of relatively large, membrane-impermeable bioactive molecules.

    • Julia F. Doerner
    • , Sebastien Febvay
    •  & David E. Clapham
  • Article
    | Open Access

    Following retinalcis/trans isomerisation, the active form of the G-protein-coupled receptor rhodopsin decays to opsin and all-trans-retinal. In this study, arrestin, a regulator of G-protein-coupled receptor activity, is shown to facilitate the concurrent sequestering of toxic all-trans-retinal and regeneration of 11-cis-retinal within the opsin population.

    • Martha E. Sommer
    • , Klaus Peter Hofmann
    •  & Martin Heck
  • Article
    | Open Access

    Fbw7 is a ubiquitin-ligase, which targets several oncoproteins for proteolysis, and is therefore important for the control and prevention of tumorigenesis. In this study, Arabi and colleagues carry out a proteomic screen of the targets of Fbw7, and identify Nuclear Factor of κ-B2 as a substrate.

    • Azadeh Arabi
    • , Karim Ullah
    •  & Olle Sangfelt
  • Article |

    Cyclic nucleotide-gated channels are apparently voltage insensitive despite having the S4-type voltage sensor. Marchesiet that the gating of wild-type CNGA1 and native CNG channels is voltage-independent in the presence of Li+, Na+ and K+, but that it is voltage-dependent in the presence of Rb+, Cs+ and organic cations.

    • Arin Marchesi
    • , Monica Mazzolini
    •  & Vincent Torre
  • Article
    | Open Access

    The activity of the Acid sensing ion channel 1, ASIC1, can be modulated by the gating modifier Psalmotoxin 1 but the molecular mechanism is unclear. Dawsonet al. report the structure of chicken ASIC1 bound to Psalmotoxin 1 and find that the toxin locks two regulatory regions of the channel into a desensitized conformation.

    • Roger J.P. Dawson
    • , Jörg Benz
    •  & Armin Ruf
  • Article
    | Open Access

    In mammalian cells, ABC transporter proteins were thought to exclusively export a range of substrates out of cells. Quazi and colleagues show that, in retinal photoreceptor cells, ABCA4 is acting as an importer of phospholipids and that mutations known to cause Stargardt disease decrease its activity.

    • Faraz Quazi
    • , Stepan Lenevich
    •  & Robert S. Molday
  • Article
    | Open Access

    Protein L-isoaspartyl methyltransferase (PIMT) is a carboxyl methyltransferase, but its role in regulating the tumour suppressor p53 is unclear. Here, PIMT is shown to methylate p53, obstructing the tumour suppressor function of p53 through reduced protein levels and stability.

    • Jae-Cheol Lee
    • , Sung-Ung Kang
    •  & Jeung-Whan Han
  • Article |

    The transport of anions across bilayer membranes is achieved by ion channel proteins, but some small molecules are also able to mediate transmembrane movement of anions. In this study, the halogen bonding of small perfluorinated molecules is shown to allow the transmembrane movement of anions.

    • Andreas Vargas Jentzsch
    • , Daniel Emery
    •  & Stefan Matile
  • Article |

    Nucleic acid superstructures are required to package genomes into the nucleus of cells. In this study, the superstructure of an RNA supercoil species is reported and is shown to be dependent on an RNA-binding protein that induces a higher level of organization compared with DNA superstructures.

    • Jason R. Stagno
    • , Buyong Ma
    •  & Xinhua Ji
  • Article |

    Poly(ADP-ribose) glycohydrolase catabolises poly(ADP-ribose), which is covalently attached to proteins following post-translational modification. In this study, the structure of poly(ADP-ribose) glycohydrolase fromTetrahymena thermophilais reported in complex with the small molecule inhibitor RBPI-3.

    • Mark S. Dunstan
    • , Eva Barkauskaite
    •  & Ivan Ahel
  • Article |

    Proteins can undergo folding while being translated by the ribosome, and the extent of this folding is influenced by the rate at which amino acids are added to the nascent chain. This study provides a framework for predicting domain folding probabilities as a function of the kinetics of amino-acid addition.

    • Edward P. O'Brien
    • , Michele Vendruscolo
    •  & Christopher M. Dobson