These short, accessible highlights summarize and contextualize must-read papers related to cell signaling. These articles add background and context to summaries of primary research. 'In brief' articles emphasize key aspects of selected articles.
 | Neuronal migration: Par6 gives the beat
Glial-guided neuronal migration is mediated by mPar6α signaling and involves a two-stroke movement of the centrosome followed by the nucleus.
Original research paper: Nature Neuroscience 7, 1195 – 1203, (2004) |
 | Nuclear organization: Migrant workers
Actively transcribed, spatially distant genes travel to sites in the nucleus that are enriched in the factors required for their transcription.
Original research paper: Nature Genetics 36, 1065 – 1071, (2004) |
 | In brief: November 2004
Cell migration | Developmental cell biology | Cell growth | Chromatin | T-cell activation | Signalling | Therapeutics | Mouse model | Plant development | Developmental biology | Gene expression | Neurodegenerative disorders | Cancer | Diabetes |
 | Cell polarity: Taking sides
The junctional adhesion molecule (JAM)-C has a key role in mouse spermiogenesis during the polarization of spermatids, by recruiting a cell-polarity complex to junctional plaques.
Original research paper: Nature 431, 320 – 324, (2004) |
 | B-cell development: Recipe for a B-cell
PU.1, EBF (early B-cell factor) and PAX5 (paired box protein 5) are ordered in a hierarchical regulatory network that directs the cell-fate specification of multipotent haematopoietic stem cells.
Original research paper: Dev. Cell 7, 607 – 617, (2004) |
 | Autoimmunity: Gene therapy for diabetes
Expression of diabetes-resistant MHC class II alleles by non-obese diabetic (NOD) mice is sufficient to prevent the development of diabetes.
Original research paper: J. Clin. Invest. 114, 969 – 978, (2004) |
 | Tumorigenesis: Divining forks for developing tumours
A new alveolar rhabdomyosarcoma mouse model sheds light on the biology of the paired box gene 3 (Pax3):forkhead (Fkhr) mutation that occurs in this rare skeletal muscle tumor.
Original research paper: Genes Dev. 18, 2614 – 2626, (2004) |
 | Developmental biology: Keeping an eye on the tempo
The insulin receptor (InR) and Tor pathways — which have a well-conserved role in controlling cell and organ size — also have the unexpected function of determining cell differentiation.
Original research paper: Cell 119, 87 – 96, (2004) |
 | Neurological disorders: The calcium link of heart and mind
Abnormal calcium signaling is implicated in autism, thus highlighting the potential therapeutic application of calcium channel blocker therapy.
Original research paper: Cell 119, 19 – 31, (2004) |
 | Cell biology of the neuron: Scaffolding at the nodes
The expression pattern of spectrins in the axonal initial segments and nodes of Ranvier reveal a new scaffolding function in neurons.
Original research paper: J. Cell Biol. 166, 983 – 990, (2004) |
 | Screening: Screen if you want to go faster!
The development of four novel label-free detection technologies may revolutionize traditional screening methods.
Original research paper: J. Biomol. Screen. 9, 467 – 480, (2004) |
 | Chemical biology: Proteins at the cross roads
Yeast proteins necessary for trafficking from the trans-Golgi network to the late endosome can easily be identified with a new cell-free assay.
Original research paper: J. Biol. Chem. 47, 48767 – 48773, (2004) |
 | Virology: Fluorescent virus lets researchers in on the Gag
A fluorescently tagged variant of HIV offers a valuable new tool for the visualization of the viral–cell interaction processes, entry and release.
Original research paper: J. Virol. 78, 10803 – 10813, (2004) |
 | Protozoan parasites: Spot the difference
The discovery of a new prokaryotic-like glyoxalase pathway in the eukaryotic parasite Leishmania major could provide a new target for rational drug design.
Original research paper: Proc. Natl Acad. Sci. USA 101, 13186 – 13191, (2004) |
 | p53 activity: Even more regulation
The methyltransferase Set9 regulates p53 activity, by a novel mechanism, through lysine methylation.
Original research paper: Nature 432, 353 – 360, (18 November 2004) |
 | DNA repair: A perfect symphony
Study of the carefully orchestrated recruitment of a large number of repair and checkpoint proteins to the site of DNA damage has given new insight into the DNA damage response.
Original research paper: Cell 118, 699 – 713, (2004) |
 | Technique: A natural view
A new biosensor has been developed that allows unlabeled, endogenous Cdc42 to be visualized in living cells.
Original research paper: Science 305, 1615 – 1619, (2004) |
 | Cytokines: Cytokine receptors take sugar
Mannoside acetylglucosaminyltransferase 5 (MGAT5) modifies cytokine-receptor N-glycans, thus regulating cytokine-mediated signaling.
Original research paper: Science 306, 120 – 124, (2004) |
 | T-cell memory: Memories are made of this...
Protective central memory T (TCM) cells, which are not dependent on the presence of parasites, can still develop in infected mice and confer immunity.
Original research paper: Nature Med. 10, 1104 – 1110, (2004) |
 | Tumorigenesis: Survivin death
Survivin, an inhibitor of apoptosis protein (IAP), localizes to the inter-mitochondrial membrane space in tumor cells and this localization accelerates tumorigenesis.
Original research paper: J. Clin. Invest. 114, 1117 – 1127, (2004) |
 | Genetics: Gains and losses
Mutations in the spindle-checkpoint gene BUB1B cause aneuploidy and contribute to an inherited cancer-predisposition syndrome.
Original research paper: Nature Genet. 36, 1159 – 1161, (2004) |
 | Yeast: a death foretold?
Older yeast cells undergo programmed cell death to allow younger cells to thrive.
Original research paper: J. Cell Biol. 166, 1055 – 1067, (2004) |
 | Systems biology: Rewiring the network
The first genome-scale study of how biological networks are rewired according to the needs of the cell, has revealed some important insights into network dynamics.
Original research paper: Nature 431, 308 – 312, (2004) |
 | Cell biology of the neuron: Reconciling trafficking models
A new model has been proposed in which NMDA (N-methyl-D-aspartate) receptor (NMDAR) clusters undergo intracellular trafficking along microtubules, which is punctuated by cycles of exocytosis and endocytosis.
Original research paper: J. Neurosci. 24, 8253 – 8264, (2004) |
 | Computational chemistry: Flexible approach to drug design
An unliganded protein structure has been successfully used as the basis of structure-based drug design (SBDD).
Original research paper: J. Am. Chem. Soc. 126, 13276 – 13281, (2004) |
 | Genomics: A golden opportunity for DNA detection
Unmodified gold nanoparticles can be used for simple and fast sequence specific detection of DNA.
Original research paper: Proc. Natl. Acad. Sci. USA 101, 14036 – 14039, (2004) |
 | Proteomics: Antibody 'sandwich' serves up phosphorylation data
Initial tests of a new antibody-based microarray strategy demonstrate the potential for the rapid analysis of protein modification states in a variety of biological samples.
Original research paper: Mol. Cell. Proteomics (8 September 2004) |
 | Shaping blood vessels: A Netrin – UNC5B affair
The repulsive netrin receptor UNC5B, expressed by endothelial tip cells, inhibits capillary branching and controls vascular system morphogenesis.
Original research paper: Nature 432, 179 – 186, ((11 November 2004)) |
 | Photosynthesis: Coming out of the dark
The identification of phytochrome-interacting factor-1 (PIF-1) provides a mechanism for the control of chlorophyll biosynthesis.
Original research paper: Science 305, 1937 – 1941, (2004) |
 | Development: Signalling a change
A new model for imaginal disc eversion in flies has wider implications for understanding the development of other organisms.
Original research paper: Developmental Cell 7, 387 – 399, (2004) |
 | Dendritic cells: Not the end of the road
Mature dendritic cells do not have to succumb to activation-induced apoptosis, but can differentiate further to a regulatory phenotype.
Original research paper: Nature Immunol. 5, 1124 – 1133, (2004) |
 | B-cell development: BCL-6 recruits new team member
MTA3 — a cell-type-specific subunit of the Mi-2/NuRD co-repressor complex — associates with BCL-6 (B-cell lymphoma 6) to inhibit the terminal differentiation of B cells to plasma cells.
Original research paper: Cell 119, 75 – 86, (2004) |
 | Ovarian cancer: Controlled aggression
The small GTPase RAB25 has now been identified as an important mediator of ovarian tumor growth and progression.
Original research paper: Nature Med. 10, 1251 – 1256, (2004) |
 | Mouse models: Inducing dormancy
MYC inactivation induces tumor regression and dormancy in liver cells.
Original research paper: Nature 431, 1112 – 1117, (2004) |
 | Gene expression: The true purpose
The nonsense mediated decay (NMD) pathway is a crucial mechanism for post-transcriptional regulation that is interlinked with essential homeostatic mechanisms in higher eukaryotes.
Original research paper: Nature Genet. 36, 1073 – 1078, (2004) |
 | Neurological disorders: Changes away from the synapse
Changes to extrasynaptic GABA (γ-aminobutyric acid) receptors in a mouse model of epilepsy could contribute to overall changes in neural excitability.
Original research paper: J. Neurosci. 24, 8629 – 8639, (2004) |
 | Rheumatoid arthritis: Halting disease in its tracks
A monoclonal antibody targeting the T-cell costimulatory molecule receptor CD137 can block rheumatoid arthritis progression in mice.
Original research paper: Nature Med. 10, 1088 – 1094, (2004) |
 | Imaging and visualization: Highlighting protein movement in living cells
A new photoactivatable fluorescent protein combines some of the best features of existing proteins used for in vivo labeling.
Original research paper: Nat. Biotechnol. 22, 1435 – 1439, (2004) |
 | Gene regulation: Leave it to cleaver
A new strategy for the modulation of ribozyme-mediated RNA cleavage may prove to be a powerful system for transgene regulation.
Original research paper: Nature 431, 471 – 476, (2004) |
 | Bacterial physiology: Under attack! SOS!
Treatment of Escherichia coli with β-lactam antibiotics induces the SOS response, which decreases the lethal effects of these bactericidal drugs and enhances E. coli survival.
Original research paper: Science 305, 1629 – 1631, (2004) |
 | Calcium signaling: NO stress for ER
Endogenously generated nitric oxide (NO) couples calcium flux changes in mitochondria to the ER stress response, resulting in upregulation of the cytoprotective chaperone Grp78.
Original research paper: Nature Cell Biology 6, 1129 – 1134, (2004) |
 | Techniques: Bright future for GFP
Green fluorescent protein (GFP) can now be used to monitor protein–protein interactions, cells that co-express different genes, and much more.
Original research paper: Cell 119, 137 – 144, (2004) |
 | Gene regulation: Reverse control
The enzyme, peptidylarginine deiminase-4 (PADI4/PAD4), previously known to deiminate histone Arg residues, has now been found to also regulate histone Arg methylation.
Original research paper: Science 306, 279 – 283, (2004) |
 | Haematopoiesis: Keeping HSCs under control
The transcription factor growth-factor independent 1 (GFI1), previously shown to promote T-cell proliferation, also restricts HSC proliferation.
Original research paper: Nature 431, 1002 – 1007, (2004) |
 | Mucosal immunology: IL-15 triggers destruction
Interleukin-15 (IL-15) coordinates the initiation of signaling pathways that lead to the killing of intestinal epithelial cells (IECs) by cytotoxic T lymphocytes (CTLs).
Original research paper: Immunity 21, 357 – 366, (2004) |
 | Early detection: Making an early mark?
Using a novel approach to analyze the methylation pattern of genes such as the tumor suppressors BRCA1 and RASSF1A, can identify individuals with ovarian cancer with 100% specificity and 82% selectivity.
Original research paper: Cancer Res. 64, 6476 – 6481, (2004) |
 | Tumour suppressors: The trials of separation
The tumor suppressor BRCA2 has a new role in regulating the fidelity of cell separation.
Original research paper: Science 306, 876 – 879, (2004) |
 | RNA silencing: Simple, but effective
A single Argonaute protein mediates both transcriptional and post-transcriptional gene silencing in Schizosaccharomyces pombe.
Original research paper: Genes Dev. 18, 2359 – 2367, (2004) |
 | Neurogenesis: Keeping an eye on the retina
The basic helix–loop–helix factor Bhlhb4 is required for the maturation — but not the initial specification — of rod bipolar (RB) cells, whereas the winged helix/forkhead transcription factor Foxn4 controls amacrine cell development.
Original research paper: Neuron 43, 779 – 793, (2004) |
 | Ion channels: Feeling the cold
For some transient receptor potential (TRP) ion channels to be maximally effective, two or more physiological stimuli must be present at the same time, indicating that they function as coincidence detectors.
Original research paper: Neuron 43, 859 – 869, (2004) |
 | Structural biology: Crystallizing the changes
The first crystal structure of an integrin in its active form has been solved.
Original research paper: Nature 2, 703 – 716, (19 Sep 2004) |
