Research Highlights

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

January 2012

• Metastasis: Signalling in transit

  

  The microenvironment of a primary tumour has been recognized as an important player in cancer progression, but whether circulating tumour cells respond to additional metastatic signals during their transit through the vasculature is unclear. Given the high concentrations of growth factors and cytokines that are contained in platelets, Labelle, Begum and Hynes proposed that, in addition to their known roles in promoting cell adhesion and protecting tumour cells from death, platelets might provide pro-metastatic signals to circulating tumour cells.

  Original research paper Nature Reviews Cancer 12 4 - 5 doi:10.1038/nrc3193

• Neuroimmunology: A CNS guard as prickly as a hedgehog

  

  Compromised function of the blood-brain barrier (BBB) and entry of activated lymphocytes into the central nervous system (CNS) are associated with the pathogenesis of neuroinflammatory diseases, such as multiple sclerosis. A recent study in Science indicates that Hedgehog signalling promotes BBB integrity and contributes to the immune-privileged state of the CNS.

  Original research paper Nature Reviews Immunology 12 4 - 5 doi:10.1038/nri3143

• Organelle dynamics: Stopping mitochondria in their tracks

  

  Damaged mitochondria can be degraded through a type of organelle-specific autophagy called mitophagy. Although the Ser/Thr kinase PTEN-induced putative kinase 1 (PINK1) and the ubiquitin E3 ligase parkin are known to promote mitophagy, their exact roles in this process were unclear. Schwarz and colleagues now show that PINK1 phosphorylates Mitochondrial RHO GTPase (MIRO), an adaptor protein that links a kinesin motor to mitochondria; this triggers the parkin-dependent degradation of MIRO to halt the movement of mitochondria, which might help target them for mitophagy.

  Original research paper Nature Reviews Molecular Cell Biology 13 4 - 5 doi:10.1038/nrm3251

• Cell signalling: Crystallizing WNT signalling

  

  Low-density lipoprotein receptor-related protein 6 (LRP6) is a co-receptor for WNT signalling that can be inhibited by the binding of Dickkopf (DKK) proteins. By solving the crystal structure of portions of the LRP6 ectodomain, in the presence or absence of the DKK1 carboxy-terminal region (DKK1-C), three studies provide insight into the conformation of LRP6 and the DKK1-mediated inhibition of WNT signalling.

  Original research paper Nature Reviews Molecular Cell Biology 13 4 doi:10.1038/nrm3260

• Neurodevelopmental disorders: A fragile synaptic balance

  

  A number of specific gene mutations are associated with intellectual disability and autism, providing hope that understanding common downstream effects might shed light on the pathophysiology of autism spectrum disorders. Bear and colleagues now show that mutations in fragile X mental retardation 1 (FMR1) and tuberous sclerosis 2 (TSC2), which are associated with similar behavioural impairments, have opposing effects on metabotropic glutamate receptor 5 (mGluR5) function and synaptic protein synthesis.

  Original research paper Nature Reviews Neuroscience 13 3 doi:10.1038/nrn3163