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.
 | Neurobiology: Sortilin apoptotic signals
The unprocessed form of nerve growth factor (proNGF) forms a signaling complex with co-receptors p75NTR and sortilin, inducing apoptosis in neuronal cells.
Original research paper: Nature 427, 843 – 848, (26 February 2004) |
 | Lipid trafficking: A new way to travel
CERT mediates the ATP-dependent ER-to-Golgi transfer of ceramide in a non-vesicular manner.
Original research paper: Nature 426, 803 – 809, (2003) |
 | In brief: February 2004
Signal Transduction | Replication | Development | Techniques | T-Cell Activation | Autoimmunity | Leukocyte Signalling | Immunological Synapses | Lymphocyte Migration | Chromosome instability | Metastasis | Neural development | Development | Neurodegenerative Disease |
 | Chromatin: Aiming for some peace and quiet
Researchers have now identified RITS (RNA-induced initiation of transcriptional gene silencing), a complex that provides a mechanistic basis for RNAi-mediated targeting of heterochromatin.
Original research paper: Science 303, 672 – 676, (2004) |
 | Antigen presentation: Regulating lipid presentation
Lipid transfer proteins, specifically saposins, have a role in editing Cd1d-bound lipids in vivo.
Original research paper: Science 303, 523 – 527, (2004) |
 | Autoimmunity: BCR and TLR9 cooperation in autoimmunity
A study has now set out to explain how autoreactive B cells are activated and the exact nature of their specificity.
Original research paper: Immunity 19, 837 – 847, (2003) |
 | Mucosal immunology: The ins and outs of gut inflammation
Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-γ and RelA.
Original research paper: Nature Immunol. 5, 104 – 112, (2004) |
 | Therapeutics: All exits blocked
A screen has been developed for compounds that prevent FOXO transport out of the nucleus and lead to cell-cycle arrest.
Original research paper: Cancer Cell 4, 463 – 476, (2003) |
 | Neurophysiology: Just a wee dram...
The BK potassium channel has a central role in behavioural responses to ethanol in C. elegans.
Original research paper: Cell 115, 655 – 666, (2003) |
 | Synaptic physiology: Putting receptors in their place
PSD95 controls AMPA receptor incorporation during long-term potentiation and experience-driven synaptic plasticity.
Original research paper: J. Neurosci. 24, 916 – 927, (2004) |
 | Bone disease: Shedding light on a silent pathway
Overexpression of 12/15-lipoxygenase might limit bone mineral density by suppressing bone formation through activation of PPAR-γ.
Original research paper: Science 303, 229 – 232, (2004) |
 | Apoptosis: Gaddgets of death
Map kinase kinase 7 (MKK7) mediates the NF-κB/GADD45β inhibition of JNK signaling, thus presenting a potential target for anti-inflammatory and anti-cancer therapies.
Original research paper: Nature Cell Biology 6, 146 – 153, (February 2004) |
 | Plant cell biology: A new size switch
A MAPKK kinase gene regulates extra–embryonic cell fate in Arabidopsis.
Original research paper: Cell 116, 109 – 119, (2004) |
 | Nuclear transport: Barring faulty exports
Nuclear retention of unspliced mRNAs in yeast is mediated by perinuclear Mlp1.
Original research paper: Cell 116, 63 – 73, (2004) |
 | Tumour immunology: STAT3 – a potential target for tumour immunotherapy
Blocking STAT3 signaling with specific inhibitors could have direct anti–tumor effects.
Original research paper: Nature Med. 10, 48 – 54, (2004) |
 | Metastasis: CAV1 connection
Overexpression of epidermal growth factor receptor causes caveolin–dependent internalization of E–cadherin, and ultimately reduces CAV1 protein levels, which activates the ß–catenin signaling pathway and downregulates E–cadherin expression.
Original research paper: Cancer Cell 4, 499 – 515, (2003) |
 | Tumour suppressors: The protective effect of arrest
The checkpoint function of p53 might be important for preserving genomic stability and so for suppressing tumorigenesis.
Original research paper: Nature Genet. 36, 63 – 68, (2004) |
 | Synaptic plasticity: Ups and downs of cerebellar plasticity
Protein phosphatase 2A inhibition induces cerebellar long-term depression and declustering of synaptic AMPA receptors.
Original research paper: Proc. Natl Acad. Sci. USA 101, 676 – 681, (2004) |
 | Receptor imaging: Making the quantum leap
The use of quantum dot ligands to visualize the movement of individual receptors in living cells has provided new insights into erbB/HER receptor-mediated signal transduction.
Original research paper: Nature Biotechnology 22, 198 – 203, (2004) |
 | Plant Cell biology:
Protein degradation protects plants
Plant responses to ethylene gas are mediated by SCFEBF1/EBF2-dependent proteolysis of EIN3 transcription factor.
Original research paper: Cell 115, 667 – 677, (2003) |
 | Apoptosis: Death by an unusual adaptor
ASC is a Bax adaptor and regulates the p53-Bax mitochondrial apoptosis pathway.
Original research paper: Nature Cell Biol. 6, 121 – 128, (2004) |
 | Natural killer cells:
New role for killer gene identified
NKG2I is an activating NK-cell receptor that has a crucial role in eliciting allograft rejection.
Original research paper: J. Exp. Med. 199, 137 – 143, (2004) |
 | Tumour suppressors:
BRCA2: preventing a breakdown
BRCA2 is required to prevent the breakdown of stalled replication forks, and disruption of this function leads to the chromosomal rearrangements that occur spontaneously in dividing BRCA2-mutant cells.
Original research paper: Genes Dev. 17, 3017 – 3022, (2003) |
 | Metastasis:
A key to metastasis
Two groups report that ezrin is upregulated in metastatic cancers, and is key to the metastatic process.
Original research paper: Nature Med. 3, 877 – 883, (4 Jan 2004) |
 | Developmental neuroscience:
Comfortably Numb
Murine Numb regulates granule cell maturation in the cerebellum.
Original research paper: Dev. Biol. 266, 161 – 177, (2004) |
 | Cytokine signaling: A TRADDitional affair
The TNF-α receptor interacting adaptor protein TRADD, a positive regulator of TNF-α signaling, inhibits the IFN-γ proinflammatory cytokine response via interaction with the STAT1-α transcription factor.
Original research paper: Nature Immunology 5, 199 – 207, (2004) |
 | Membrane fusion: Fine-tuning
A new functional class of SNARE proteins – inhibitory (i)-SNAREs – that fine-tune the specificity of membrane fusion has been identified.
Original research paper: J. Cell Biol. 164, 79 – 88, (2004) |
 | Reproductive immunology: Role of complement in pregnancy loss
Two studies have now defined the role of complement components in pregnancy loss, using two different model systems.
Original research paper: Immunity 19, 813 – 822, (2003) |
 | Tumour immunity: Throwing LIGHT on tumour rejection
Tumor rejection can be stimulated by priming naive T cells inside tumors with LIGHT – a member of the tumor necrosis factor family.
Original research paper: Nature Immunol. 5, 141 – 149, (2004) |
 | Proteomics: Interacting maps
Large-scale protein–protein interaction maps, or interactomes, have been reported for both Drosophila melanogaster and C. elegans.
Original research paper: Science 302, 1727 – 1736, (2003) |
 | Anticancer drugs: Unleashing p53
Small-molecule antagonists of the MDM2–p53 interaction activate the p53 pathway in cancer cells and inhibit tumor growth in mice.
Original research paper: Science 303, 844 – 848, (2004) |
