Short, accessible synopses of recent important articles concerning signalling pathways.
Mammalian cells respond to physical forces through chemical signalling networks. Salaita et al. set out to elucidate the mechanisms of this chemo-mechanical coupling, and reveal that the spatial organization of receptors can affect downstream cellular responses to ligands.
Original research paper Nature Reviews Molecular Cell Biology 11 311 doi:10.1038/nrm2884
The hormone leptin is well known for its role in energy homeostasis, but it has also been found to influence synaptic plasticity. Investigating the mechanisms that underlie this function, Moult et al. now show that leptin induces glutamate receptor 1 (GluR1) expression at hippocampal synapses and increases synaptic strength by inhibiting the protein phosphatase and tensin homologue (PTEN).
Original research paper Nature Reviews Neuroscience 11 298 doi:10.1038/nrn2844
The ubiquitin ligase SKP2, which is part of the SKP1–CUL1–F-box (SCF) complex, has been implicated in tumorigenesis owing to its capacity to degrade the tumour suppressor p27, a cyclin-dependent kinase (CDK) inhibitor. Pier Paolo Pandolfi and colleagues have found that the loss of SKP2 can promote senescence in response to oncogene activation through a pathway involving expression of p27.
Original research paper Nature Reviews Cancer 10 314 doi:10.1038/nrc2845
Tumour cells can promote their survival by shifting the host immune response from immunogenic to tolerogenic. Melody Swartz and colleagues have shown that tumours can do this by exploiting a pathway that is normally involved in maintaining tolerance in the lymph node stroma.
Original research paper Nature Reviews Cancer 10 314 - 315 doi:10.1038/nrc2847
Epilepsy is a chronic neurological disorder in which affected individuals suffer from recurring, unprovoked seizures. There is evidence to suggest that inflammatory processes can promote seizures, and damage to the brain following neurotrauma, stroke or infection is associated with a high risk of developing epilepsy. Now, a study in Nature Medicine has shown that the chromatin component high-mobility group box 1 (HMGB1), an endogenous Toll-like receptor 4 (TLR4) ligand, is released by stressed neurons and glial cells and has proconvulsant effects.
Original research paper Nature Reviews Immunology 10 291 doi:10.1038/nri2767