Research Highlights

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

August 2011

• Innate immunity: SHP regulates TLR signalling

  

  Several negative regulatory mechanisms that control Toll-like receptor (TLR) signalling have been described. Reporting in Nature Immunology, Jo and colleagues now add the orphan nuclear receptor SHP (small heterodimer partner; also known as NR0B2) to the list of intrinsic negative regulators of TLR-dependent inflammatory responses.

  Original research paper Nature Reviews Immunology 11 502 - 503 doi:10.1038/nri3031

• Cell migration: Many (converging) pathways, one destination

  

  Elucidating how the ever-increasing number of pathways that reportedly affect cell migration are spatially and temporally regulated to influence the molecular migration machinery is a challenge. For example, how does RALB signalling to the exocyst complex, which controls secretory vesicle trafficking, regulate cell motility? Mechanisms that are likely to contribute to migration have been described, but Parrini et al. now report a direct link between the RALB-exocyst pathway and the small GTPase RAC1.

  Original research paper Nature Reviews Molecular Cell Biology 12 465 doi:10.1038/nrm3163

• Cell cycle: Keeping centrosome numbers in check

  

  Centrosomes need to duplicate once per cell cycle to ensure that their numbers remain stable in the daughter cells. Malek and colleagues now delineate a pathway that regulates duplication and ensures it is synchronized with the cell cycle.

  Original research paper Nature Reviews Molecular Cell Biology 12 466 - 467 doi:10.1038/nrm3158

• Pain: Blocking painful interactions

  

  The neuronal voltage gated calcium channel Cav2.2 is an established contributor to many persistent pain syndromes; however, existing calcium channel blockers are relatively non-specific and result in undesirable side effects. A paper published in Nature Medicine now reveals a new approach to target the function of Cav2.2 using a small synthetic peptide, alleviating inflammatory and neuropathic pain with minimal adverse effects.

  Original research paper Nature Reviews Neuroscience 12 431 doi:10.1038/nrn3069

• T cells: A metabolic sHIFt to turn 17

  

  Naive T cells are known to upregulate glycolysis when they differentiate into effector T cells, and they subsequently rely on this pathway to produce ATP. By contrast, recent findings have indicated that the generation of induced regulatory T (T_Reg) cells does not involve this metabolic switch. However, the mechanisms that link cellular metabolism with immune signalling and cell fate have not been fully deciphered. A new study shows that the transcription factor hypoxia-inducible factor 1α (HIF1α) is required for the metabolic changes that occur in differentiating T helper 17 (T_H17) cells and thus can alter the balance between T_H17 and induced T_Reg cell generation.

  Original research paper Nature Reviews Immunology 11 503 doi:10.1038/nri3037