Research Highlights

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

October 2009

• 'Blue' lighting cell signaling research

  

  By fusing a light-sensitive domain of an oat plant protein to Rac1, researchers created a genetically encoded protein fusion that can be reversibly activated with blue light and control cell movement—an attractive alternative to current caging tools.

  Original research paper Nature Methods 6 694 - 695 doi:10.1038/nmeth1009-694a

• Cell signalling: Free ubiquitin!

  

  The E3 ubiquitin ligase TNF receptor-associated factor 6 (TRAF6) is known to activate nuclear factor-κB (NF-κB) downstream of the interleukin-1 and Toll-like receptors. Together with the ubiquitin-conjugating E2-type enzymes UBC13 and UEV1A (also known as UBE2V1), TRAF6 catalyses Lys63-linked ubiquitylation, which stimulates phosphorylation and activation of TGFβ-activated kinase 1 (TAK1; also known as MAP3K7), consequent phosphorylation of IκB kinase (IKK) and activation of NF-κB. In Nature, Zhijian Chen and colleagues now report on the mechanism of TRAF6-mediated NF-κB activation: TRAF6 generates unanchored polyubiquitin chains that bind to the regulatory subunits of the TAK1 and IKK complexes, leading to the activation of these kinases.

  Original research paper Nature Reviews Molecular Cell Biology 10 653 doi:10.1038/nrm2765

• Regulatory T cells: Eos: the sound of silence

  

  Naturally occurring CD4⁺CD25⁺ regulatory T (T_Reg) cells are essential for maintaining immune homeostasis and the transcription factor forkhead box P3 (FOXP3) is required for their suppressive function. Although much is known about the mechanisms of FOXP3-mediated gene induction in T_Reg cells, the molecular mechanisms of FOXP3-dependent gene repression are largely unknown. Pan et al. now show that the interaction of FOXP3 with Eos (also known as Ikzf4), a zinc finger transcription factor of the Ikaros family, is required for FOXP3-mediated gene repression in T_Reg cells and for the suppressive activity of T_Reg cells.

  Original research paper Nature Reviews Immunology 9 674 - 675 doi:10.1038/nri2639

• γδ T cells: Innate source of IL-17

  

  Interleukin-17 (IL-17) has been the subject of a great deal of recent research, mainly as the cytokine that characterizes the CD4⁺ T helper cell subset known as T_H17 cells. Now, two studies published in Immunity show that γδ T cells are also an important source of IL-17, which is produced by these cells without ligation of their T cell receptor (TCR) and contributes to a first line of defence against pathogens and to the early stages of autoimmune inflammation.

  Original research paper Nature Reviews Immunology 9 671 doi:10.1038/nri2645

• Dendritic cells: One SIGN, different paths

  

  When an invading pathogen meets a dendritic cell (DC) it is greeted by several cell surface receptors that work together to tailor a fitting immune response. A new report published in Nature Immunology reveals how one receptor creates further specificity by altering cytokine production levels in response to binding particular pathogen carbohydrates.

  Original research paper Nature Reviews Immunology 9 676 doi:10.1038/nri2640