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A 3D projection of the anchor cell in C. elegans (magenta) as it invades through the basement membrane (green) and into the vulval epithelium. The UNC-6 (netrin) pathway polarizes the anchor cell and orients it for invasion.p 183
The double anniversary of Darwin's bicentenary and 150 years since publication of On the Origin of Species by Means of Natural Selection provides the perfect pretext to enhance the public understanding of evolution.
Cytokinesis ensures proper partitioning of genomic and cytoplasmic material between dividing cells. A key regulator of this process is the centralspindlin complex. Two recent papers report that GAP activity of one of the members of this complex regulates the function of Rho family GTPases during cytokinesis.
Deposition of amyloid β-peptide in cerebral vessel walls, termed cerebral amyloid angiopathy (CAA), enhances the cognitive deficits associated with Alzheimer's disease. The molecular details by which circulatory defects with hypoxia alter peptide clearance, contributing to brain deposition and AD, are beginning to be elucidated.
Metazoan cells respond to external stress or infection through multiple signalling pathways that converge on NF–κB activation, initiating a program designed to promote survival or trigger cell death. Recent evidence reveals a mechanism for NF-κB activation that requires assembly of linear polyubiquitin chains as scaffolds to recruit the activation complex.
In the classical view, adult stem cells and their differentiating progeny are considered to be distinct entities in an irreversible sequence of development. However, emerging evidence suggests that this distinction may not be so definitive. Recent work in the mouse shows that a population of differentiating spermatogonia, when transplanted, can 'de-differentiate' into functional self-renewing stem cells.
NF-κB signalling protein NEMO is the first physiological substrate for linear head-to-tail polyubiquitin chains. The heterodimeric ubiquitin ligase LUBAC catalyses the reaction and mice lacking a LUBAC subunit show defects in NF-κB signalling.
Pin1 interacts with Notch1 to increases its cleavage by γ-secretase and thus its transcriptional activity. In a feedback loop, Notch1 controls Pin1 expression, which results in enhanced Notch1 tumorigenic activity.
Accumulation of amyloid β peptide in cerebral blood vessels has been linked to brain dysfunction. SRF and myocardin transcription factors are induced by cerebral hypoxia and reduce amyloid clearance by regulating SREBP2, a transcriptional repressor that acts on the amyloid aggregate clearance factor LRP1.
RCAN1, the regulator of calcineurin phosphatase, interacts with TAK1 kinase binding protein 2 (TAB2). This leads to formation of the signalling complex TAK1-TAB1-TAB2, which phosphorylates RCAN1 and converts it to an activator of the calcineurin-NFAT pathway. Activated calcineurin then switches the signal off by dephopshorylating TAK1 and TAB1.
The intracellular fragment of the adhesion molecule EpCAM, which is generated by the proteases TACE and presenilin-2, increases cell proliferation and acts in a complex with β-catenin and Lef-1 to regulate gene expression.
The DNA-binding chromodomain helicase CHD8 regulates gene expression but how it acts on specific genes has been unclear. During early embryogenesis in mice, CHD8 recruits histone H1 to the p53-dependent promotors of apoptotic genes and thereby prevents massive cell death at this stage of development.
The C.elegans anchor cell is a model for cellular invasion through the basement membrane. Now netrin (UNC-6) is found to polarize the actin regulators Ena/VASP and PtdIns (4,5)P2 towards the basement membrane to promote anchor cell invasion.
When transplanted into adult mice, purified mouse spermatogonial progenitors that are committed to differentiation can revert to functional germinal stem cells, with the ability to repopulate germ-cell-depleted testes.
Separation of intertwined sister chromatids, mediated by topoisomerase II, is essential for mitosis. In a separate mechanism, phosphorylation of topoisomerase II at Ser 1524 during the G2/M phase of the cell cycle recruits MDC1 to activate the decatenation checkpoint required for genomic stability.
CDK5 kinase regulates the neuronal stress response, whereas the DNA damage response kinase ATM induces apoptosis in postmitotic neurons. Now, CDK5 activated by DNA damage is shown to directly activate ATM to induce neuronal cell death.
Fibrillar polyglutamine aggregates are taken up by mammalian cells in culture and associate with aggresomes that contain both proteasome subunits and chaperones. Aggresomes also recruit soluble proteins that share the same amyloidogenic sequences as the internalised polyglutamine aggregates.
