Research Highlights

Short, accessible synopses of recent important articles concerning signalling pathways.

January 2008

• Signalling: The ins and outs of Ca²⁺ signalling in mast cells

  

  The influx of calcium ions (Ca²⁺) through calcium-release-activated calcium (CRAC) channels following the engagement of immunoreceptors on lymphocytes is widely recognized as being crucial for the proper functioning of these cells. Ca²⁺ influx is understood to be triggered by the depletion of Ca²⁺ stores in the endoplasmic reticulum (ER), a process that is referred to as store-operated Ca²⁺ (SOC) influx. Recently, two key regulators of Ca²⁺ influx have been identified – stromal interaction molecule 1 (STIM1), which is a sensor of ER Ca²⁺ stores that couples depletion of Ca²⁺ from ER stores with SOC influx, and ORAI1 (also known as CRACM1), which is a component of the CRAC channel. Now, two studies report for the first time on the role of these molecules in regulating mast-cell function.

  Original research paper Nature Reviews Immunology 8 6 - 7 doi:10.1038/nri2245

• Lymphocyte development: SLAM dunk for innate T cells

  

  Conventional T cells are selected in the thymus by recognition of peptide–MHC complexes on thymic epithelial cells. By contrast, subsets of T cells with innate-like characteristics can arise in the thymus by selection on thymocytes. Three recent reports in Immunity describe the requirements for the development of various thymocyte-selected, innate-like T-cell subsets and reveal a common need for signalling through the SLAM (signalling lymphocytic activation molecule) family of receptors.

  Original research paper Nature Reviews Immunology 8 3 doi:10.1038/nri2243

• Cell migration: Follow the leader!

  

  How tumour cells invade the surrounding tissue remains an open question in cancer biology. Although various models exist, a popular concept being the epithelial-to-mesenchymal transition, Erik Sahai and colleagues now provide evidence for an alternative mechanism of epithelial cell invasion that does not involve transition to a mesenchymal state. Instead, squamous cell carcinoma (SCC) cells that retain epithelial characteristics exploit the matrix-remodelling ability of nearby mesenchymal cells and follow in their tracks.

  Original research paper Nature Reviews Cancer 8 5 doi:10.1038/nrc2298

• Tumour suppressors: Keeping Trim

  

  Hepatocellular carcinoma (HCC), a relatively common cancer worldwide, can be induced by many different stimuli. Régine Losson and colleagues have found that in mice one tumour-suppressor gene, tripartate motif-containing 24 (Trim24), seems to specifically restrict the genesis of HCC through regulating the retinoic acid (RA) transcriptional network.

  Original research paper Nature Reviews Cancer 8 8 - 9 doi:10.1038/nrc2300

• DNA damage: Conducting repair

  

  The DNA-damage response (DDR) signalling network mediates context-specific DNA repair, cell cycle checkpoint activation and/or apoptosis. DNA double-strand breaks (DSBs) cause DDR proteins to redistribute into dynamic, higher-order multiprotein assemblies on the surrounding chromatin. Adaptor proteins are crucial to build these assemblies in a spatial and temporal manner. This is achieved, in part, by hierarchical phosphorylations that are selectively recognized by downstream DDR proteins. Three separate papers, by Huen et al., Mailand et al. and Kolas et al., show that ubiquitylation of the chromatin that surrounds DSBs also contributes to orchestration of the DDR.

  Original research paper Nature Reviews Molecular Cell Biology 9 6 - 7 doi:10.1038/nrm2323