Cell biology articles within Nature

Featured

  • News & Views |

    An exceptionally large-scale project aimed at assigning function to all protein-coding genes in the human genome is reported on page 721 by Neumann et al.1. Here are two complementary views on the experimental design and analysis, and on how useful the findings will be to cell biologists.

    • Jason R. Swedlow
    • , Cecilia Cotta-Ramusino
    •  & Stephen J. Elledge

  • Letter |

    Cancer 'chemoprevention' uses substances to reverse, suppress or prevent the initial phase of carcinogenesis or the progression of neoplastic cells to cancer cells. Here it is shown that treatment with TRAIL proteins and all-trans-retinyl acetate can cause the death, in vitro and in vivo, of premalignant cells deficient in the adenomatous polyposis coli gene. Normal cells are unaffected. Selectively eliminating premalignant tumour cells in this way is thus an effective method for chemoprevention.

    • Ling Zhang
    • , Xiaoyang Ren
    •  & Xiangwei Wu

  • Letter |

    Making haploid plants — which inherit chromosomes from only one parent — is useful for genetic research and also, crucially, for plant breeding. A new method for generating haploid Arabidopsis plants is now described, involving the manipulation of a single centromeric protein, CENH3. When cenh3 null plants are crossed with wild-type plants, the mutant chromosomes are eliminated, producing haploid progeny.

    • Maruthachalam Ravi
    •  & Simon W. L. Chan

  • Article |

    Zscan4 is shown to be involved in maintaining telomeres in embryonic stem (ES) cells. Only 5% of ES cells express Zscan4 at a given time, but nearly all ES cells activate Zscan4 at least once within nine passages. The transient Zscan4-positive state is associated with rapid telomere extension by telomere recombination and upregulation of meiosis–specific homologous recombination genes. Knocking down Zscan4 shortens telomeres, increases karyotype abnormalities and spontaneous sister chromatid exchange, and slows down cell proliferation until reaching crisis by eight passages.

    • Michal Zalzman
    • , Geppino Falco
    •  & Minoru S. H. Ko

  • Article |

    Here, multivesicular body (MVB) biogenesis is reconstituted using giant unilamellar vesicles and all of the ESCRT complexes. ESCRT-0 is required for clustering of cargo proteins, whereas ESCRT-I and -II in combination deform the membrane into buds, in which cargo is confined. ESCRT-III subunits localize to the bud neck and are required for scission of the membrane to form intraluminal vesicles. These results explain how ESCRT complexes sequester cargo proteins into MVBs.

    • Thomas Wollert
    •  & James H. Hurley

  • Letter |

    In multicellular organisms, apoptotic cells are removed from tissues by phagocytes, which recognize and engulf the dying cells. The molecular mechanisms underlying the subsequent degradation of the cells have been unclear. Here, two evolutionarily conserved genes have been identified that are required for such processing in Caenorhabditis elegans and mammals. An understanding of these events could lead to new treatments for diseases associated with poor engulfment and destruction of dying cells.

    • Jason M. Kinchen
    •  & Kodi S. Ravichandran

  • Article |

    Cellular senescence — an irreversible cell-cycle arrest — has been implicated in suppressing tumour formation or growth. A new cellular signalling pathway that drives senescence has now been identified. This pathway does not involve most known mediators of senescence, and instead signals via the proteins Atf4, p27 and p21. Inactivating the proto-oncogene Skp2 in the context of oncogenic signalling can induce senescence through this new pathway, indicating that drugs that target Skp2 might be useful in cancer treatment.

    • Hui-Kuan Lin
    • , Zhenbang Chen
    •  & Pier Paolo Pandolfi

  • News & Views |

    The front of motile cells is thought to be pushed out by branched filaments of actin protein abutting the cell membrane. New work challenges this textbook view, showing that actin branches grow away from, or obliquely to, a surface.

    • Cécile Sykes
    •  & Julie Plastino

  • News & Views |

    Cellular senescence is a physiological mechanism for thwarting the proliferation of tumour cells. Encouraging cancer-prone cells to senesce might therefore be a way to nip this disease in the bud.

    • Manuel Serrano

  • Letter |

    The amino-terminal tails of histone proteins are subject to a variety of post-translational modifications; addition or removal of these 'marks' facilitates gene activation or silencing. Here, a mechanism is defined that modulates the activity of the dual-specificity histone demethylase LSD1 during androgen-dependent transcription. Androgen-dependent signalling through protein kinase C beta I leads to phosphorylation of a histone amino acid, which prevents demethylation of an adjacent amino acid by LSD1.

    • Eric Metzger
    • , Axel Imhof
    •  & Roland Schüle

  • Letter |

    Signalling through the epidermal growth factor receptor (EGFR) is preceded by its dimerization, which has typically been thought to occur through a ligand-induced conformational change. Here, the dimerization dynamics of individual EGFR molecules have been determined in living cells in real time, using a quantum-dot-based approach. Unliganded EGFR molecules undergo spontaneous and reversible dimerization; these pre-formed dimers are primed for ligand binding and signalling and are enriched at the cell periphery.

    • Inhee Chung
    • , Robert Akita
    •  & Ira Mellman

  • Article |

    A new strategy is presented to accurately profile the activity of human genes in endocytosis by combining genome-wide RNAi, automated high-resolution confocal microscopy and quantitative multi-parametric image analysis. Several novel components of endocytosis and endosome trafficking were uncovered; a systems analysis further revealed that the cell regulates the number, size and concentration of cargo within endosomes.

    • Claudio Collinet
    • , Martin Stöter
    •  & Marino Zerial

  • Brief Communications Arising |

    • François Majo
    • , Ariane Rochat
    •  & Yann Barrandon

  • News & Views |

    Although sphingolipids are vital cellular components, the path to their production is paved with toxic intermediates. Orm proteins allow cells to form these lipids without killing themselves in the process.

    • Fikadu G. Tafesse
    •  & Joost C. M. Holthuis

  • Letter |

    Evolution from one fitness peak to another must involve either transitions through intermediates of low fitness or skirting round the fitness valley through compensatory mutations elsewhere. Here, the base pairs in mitochondrial tRNA stems is used as a model to show that deep fitness valleys can be traversed. Transitions between AU and GC pairs have occurred during mammalian evolution without help from genetic drift or mutations elsewhere.

    • Margarita V. Meer
    • , Alexey S. Kondrashov
    •  & Fyodor A. Kondrashov

  • Letter |

    Peptide hormones such as oxytocin and vasopressin influence social behaviour in several mammalian species. Here it is shown that a population of interneurons in the rat olfactory bulb releases vasopressin, and that vasopressin signalling is required in the olfactory system for proper social recognition in rats. Although vasopressin may not work in exactly the same way in humans, social recognition mediated by experience-dependent vasopressin release may be common.

    • Vicky A. Tobin
    • , Hirofumi Hashimoto
    •  & Mike Ludwig

  • Letter |

    The RAS–RAF signalling pathway is an attractive target for drug development in oncology, and several RAF inhibitors are being tested in clinical trials. Here and in an accompanying paper, RAF inhibitors are shown to have opposing roles, functioning as either inhibitors or activators of RAF depending on the cellular context and mutational status of RAF. The mechanistic basis for these opposing roles is dissected. The results have implications for the clinical use of these inhibitors and for the design of kinase inhibitors.

    • Poulikos I. Poulikakos
    • , Chao Zhang
    •  & Neal Rosen

  • Letter |

    The existence of all-female species of whiptail lizard, formed as a hybrid between sexual species, has been known since 1962; however, how the meiotic program is altered to produce diploid eggs while maintaining heterozygosity has remained unclear. Here it is shown in parthenogenetic species that meiosis initiates with twice the number of chromosomes compared to sexual species, and that pairing and recombination takes place between genetically identical sister chromosomes instead of between homologues.

    • Aracely A. Lutes
    • , William B. Neaves
    •  & Peter Baumann

  • Letter |

    The vertebrate body plan shows marked bilateral symmetry, although this can be disrupted in conditions such as scoliosis. Here, a mutation in Rere is found that leads to the formation of asymmetrical somites in mouse embryos; furthermore, Rere is shown to control retinoic acid signalling, which is required to maintain somite symmetry by interacting with Fgf8. The results provide insight into how bilateral symmetry is maintained.

    • Gonçalo C. Vilhais-Neto
    • , Mitsuji Maruhashi
    •  & Olivier Pourquié

  • Letter |

    Here, iPS cell technology is used to study the mechanisms underlying dyskeratosis congenita in humans. Reprogramming restores telomere elongation in dyskeratosis congenita cells despite genetic lesions affecting telomerase. The reprogrammed cells were able to overcome a critical limitation in telomerase RNA component (TERC) levels to restore telomere maintenance and self-renewal, and multiple telomerase components are targeted by pluripotency-associated transcription factors.

    • Suneet Agarwal
    • , Yuin-Han Loh
    •  & George Q. Daley

  • Letter |

    Plants and animals sense intruding pathogens by using proteins that recognize diverse microbe-associated molecular patterns (MAMPs) and initiate innate immune responses. Early signalling responses in the host include calcium influx, an oxidative burst and transcriptional reprogramming. Here, four calcium-dependent protein kinases are described that function as calcium sensors, act as convergence points for various MAMPs, and are crucial for transcriptional reprogramming and oxidative burst in plants.

    • Marie Boudsocq
    • , Matthew R. Willmann
    •  & Jen Sheen

  • Letter |

    Semaphorins and their receptors, plexins, relay guidance information to neurons during development and regulate actin dynamics through an unknown mechanism. Recently, proteins of the Mical family of enzymes have been found to associate with plexins; here, Mical is reported to directly link semaphorins and their plexin receptors to the precise control of actin filament dynamics.

    • Ruei-Jiun Hung
    • , Umar Yazdani
    •  & Jonathan R. Terman

  • News & Views |

    Defects in mitochondria are implicated in Parkinson's disease. Study of a quality-control pathway involving the proteins PINK1 and Parkin provides further clues about the mechanism involved.

    • Asa Abeliovich

  • Letter |

    Ca2+ channels and calmodulin (CaM) are two prominent hubs of biological signalling networks, affecting functions such as cardiac excitability and gene transcription. The prevailing view has been that the ultrastrong affinity of channels for the Ca2+-free form of calmodulin (apoCaM) ensures their saturation with CaM and yields a form of concentration independence between Ca2+ channels and CaM. Here, however, significant exceptions to this autonomy are shown to exist.

    • Xiaodong Liu
    • , Philemon S. Yang
    •  & David T. Yue

  • Article |

    To survive and evade host responses, malaria parasites export several hundred proteins into the host cell on infection. A feature of these proteins is a conserved, pentameric motif that is cleaved by an unknown protease before export. This is one of two independent studies revealing the identity of the protease as plasmepsin V, an aspartic acid protease located in the endoplasmic reticulum. This enzyme is essential for parasite viability and is an attractive candidate for drug development.

    • Ilaria Russo
    • , Shalon Babbitt
    •  & Daniel E. Goldberg

  • Article |

    To survive and evade host responses, malaria parasites export several hundred proteins into the host cell on infection. A feature of these proteins is a conserved, pentameric motif that is cleaved by an unknown protease before export. This is one of two independent studies revealing the identity of the protease as plasmepsin V, an aspartic acid protease located in the endoplasmic reticulum. This enzyme is essential for parasite viability and is an attractive candidate for drug development.

    • Justin A. Boddey
    • , Anthony N. Hodder
    •  & Alan F. Cowman

  • Letter |

    Chronic myeloid leukaemia is caused by a BCR-ABL fusion, a constitutively active tyrosine kinase that, it is believed, leads to suppression of the forkhead O transcription factors (FOXO). Although the use of the tyrosine kinase inhibitor imatinib is a breakthrough for CML therapy, imatinib does not deplete the leukaemia-initiating cells (LICs) that drive the recurrence of CML. Foxo3a is now shown to have an essential role in the maintenance of CML LICs in a mouse model.

    • Kazuhito Naka
    • , Takayuki Hoshii
    •  & Atsushi Hirao

  • Letter |

    Heterozygous mutations in the gene encoding CHD7, an ATP-dependent chromatin-remodelling protein, result in CHARGE syndrome — a disorder characterized by malformations of the craniofacial structures, peripheral nervous system, ears, eyes and heart. In humans and Xenopus, CHD7 is now shown to be essential for the formation of multipotent migratory neural crest and for activating the transcriptional circuitry of the neural crest; shedding light on the pathoembryology of CHARGE syndrome.

    • Ruchi Bajpai
    • , Denise A. Chen
    •  & Joanna Wysocka

  • Letter |

    The RAS–RAF signalling pathway is an attractive target for drug development in oncology, and several RAF inhibitors are being tested in clinical trials. Here and in an accompanying paper, RAF inhibitors are shown to have opposing roles, functioning as either inhibitors or activators of RAF depending on the cellular context and mutational status of RAF. The mechanistic basis for these opposing roles is dissected. The results have implications for the clinical use of these inhibitors and for the design of kinase inhibitors.

    • Georgia Hatzivassiliou
    • , Kyung Song
    •  & Shiva Malek

  • News & Views |

    Damaged lysosomes, the principal degradative organelles, can kill a cell. A stress-induced protein controls lysosome stability, providing a potential target to treat lysosome-related diseases and cancer.

    • Ibolya Horváth
    •  & László Vígh

  • Letter |

    Heat shock protein 70 (Hsp70) is a molecular chaperone which, by inhibiting lysosomal membrane permeabilization, promotes the survival of stressed cells. Hsp70 is now shown to stabilize lysosomes by binding to an anionic phospholipid, BMP, resulting in stimulation of acid sphingomyelinase (ASM) activity. Notably, the decreased ASM activity and lysosomal stability seen in patients with Niemann–Pick disease can be corrected by treatment with recombinant Hsp70.

    • Thomas Kirkegaard
    • , Anke G. Roth
    •  & Marja Jäättelä

  • News & Views |

    Physics provides new approaches to difficult biological problems: a plausible mathematical model of how cilia and flagella beat has been formulated, but it needs to be subjected to rigorous experimental tests.

    • T. J. Mitchison
    •  & H. M. Mitchison

  • News & Views |

    By synchronizing clocks, humans make more efficient use of their time and orchestrate their activities in different places. Bacteria have now been engineered that similarly coordinate their molecular timepieces.

    • Martin Fussenegger

  • Letter |

    Kinase regulatory pathways are used in eukaryotic DNA replication to facilitate coordination with other processes during cell division cycles and response to environmental cues. The Dbf4–Cdc7 kinase (DDK) is one of at least two cell-cycle-regulated protein kinase systems essential for initiation of DNA replication. DDK is now shown to relieve the inhibitory activity of the amino-terminal domain of the replicative helicase Mcm4, thus promoting S phase.

    • Yi-Jun Sheu
    •  & Bruce Stillman

Browse broader subjects

Browse narrower subjects

Browse Cell biology across other nature.com journals