Research Highlights

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

April 2009

• Calcium: InsP₃ hosts a receptor get-together

  

  Intracellular Ca²⁺ concentration is regulated in part by the activity of inositol-1,4,5-trisphosphate (InsP₃) receptors (InsP₃Rs). InsP₃R tetramers function as Ca²⁺ channels that release Ca²⁺ from the endoplasmic reticulum in response to InsP₃ and Ca²⁺. Low concentrations of InsP₃ can stimulate a 'blip' of Ca²⁺ release from a single InsP₃R channel; the Ca²⁺ released then stimulates additional InsP₃Rs, generating a 'puff' of Ca²⁺. This puff of Ca²⁺ feeds forward to stimulate subsequent waves of Ca²⁺ release as InsP₃ and Ca²⁺ concentrations increase. However, the biochemical mechanism that underlies receptor clustering and the escalating response to InsP₃ and Ca²⁺ is not fully understood. Colin Taylor and colleagues now report in Nature that InsP₃ promotes receptor clustering, which tunes receptor sensitivity to InsP₃ and Ca²⁺ to regulate channel activity.

  Original research paper Nature Reviews Molecular Cell Biology 10 10 238 - 239 doi:10.1038/nrm2660

• Cytoskeleton: N-WASP turnover: the sting in the actin tail

  

  ARP2/3 complex activity is crucial for the reorganization of the actin cytoskeleton at the cell cortex during events such as vesicular trafficking, pathogen infection and cell movement. The study of pathogens undergoing actin-based motility has provided insight into how this activity is regulated. Now, Michael Way and colleagues show that ARP2/3-complex-dependent motility of vaccinia virus is controlled by the dynamic interaction between neuronal Wiskott–Aldrich syndrome protein (N-WASP) and growing actin filaments.

  Original research paper Nature Reviews Molecular Cell Biology 10 10 240 - 241 doi:10.1038/nrm2661

• Signal transduction: Deleting PTEN for better or worse

  

  Manipulating neurogenesis could have a role in the treatment of both neurodevelopmental disorders and neurodegenerative diseases. Two new studies show that PTEN (phosphatase and tensin homolog) and its downstream signalling pathway might be promising targets for developing such treatments.

  Original research paper Nature Reviews Neuroscience 10 10 248 - 249 doi:10.1038/nrn2625

• T-cell responses: Directing responses in death

  

  It is well established that different combinations of cytokines drive the differentiation of CD4⁺ T cells into specialized effector-cell subsets. For example, both transforming growth factor-β (TGFβ) and interleukin-6 (IL-6) are required for the generation of IL-17-producing T helper 17 (T_H17) cells, and IL-23 supports the clonal expansion of these cells. These conditions can be easily recreated in vitro, but it is not clear what events trigger the simultaneous production of these cytokines in vivo. Now, Torchinsky et al. show that infected apoptotic cells induce dendritic cells (DCs) to establish the ideal conditions for T_H17-cell differentiation in vivo.

  Original research paper Nature Reviews Immunology 9 9 222 doi:10.1038/nri2538

• Migration: Calcium influx is moving

  

  Store-operated Ca²⁺ influx is known to be involved in cancer cell migration, but the finer molecular details of this process have yet to be mapped out. Xin-Yun Huang and colleagues have investigated the function of two known regulators of Ca²⁺ influx and found their function to be essential for breast cancer metastasis.

  Original research paper Nature Reviews Cancer 9 9 230 - 231 doi:10.1038/nrc2629