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The Cvt pathway in yeast operates constitutively, but the mechanism by which non-cargo material is excluded from the vacuole is incompletely defined. Martens and colleagues show that cargo binding to the cargo receptor Atg19 exposes further Atg8 binding sites on the receptor, which draws the isolation membrane around the autophagic cargo and prevents inclusion of non-cargo material in autophagosomes.
The surface area of neurons increases rapidly during neurite extension. Galli and colleagues show that the endoplasmic reticulum (ER)-resident SNARE protein Sec22b bridges the ER and plasma membrane during this process and contributes to plasma membrane expansion, but does not promote membrane fusion.
Genetically encoded and post-translationally generated variations of tubulin C-terminal tails give rise to extensive heterogeneity of the microtubule cytoskeleton. The generation of different tubulin variants in yeast now demonstrates how single amino-acid differences or post-translational modifications can modulate the behaviour of selected molecular motors.
Although human cancers exhibit intratumour heterogeneity, the influence of the tumour environment on this property is unclear. Single basal-like mammary epithelial cells are now shown to engage a dynamic TGFBR3–JUND signalling circuit in an extracellular-matrix-dependent manner. Cell transition between the distinct gene expression states underlying this circuit alters their properties and may modulate their propensity to malignancy.
New blood vessels sprout from existing vasculature to ensure vascularization of developing organs and tissues. A combination of computational modelling and experimental analysis shows that sprout elongation is mediated by differential adhesion dynamics among endothelial cells. The adhesiveness of an individual endothelial cell is governed by VEGF and Notch signalling.
Repair of a chromosome break can result in part of a chromosome attaching to a different chromosome, causing gene deregulation and disease. Roukos and Misteli discuss the spatial aspect of chromosome translocation and the role of DNA repair pathways in this process.
Endothelial cells undergo rearrangements during angiogenic sprouting. Gerhardt and colleagues show that the flux in Notch signalling levels in individual cells of sprouting vessels results in differential dynamics of VE-cadherin at junctions to drive functional endothelial cell rearrangements during sprouting. They also find that differential VE-cadherin dynamics are affected in retinopathy and tumour vessels.
Janes and colleagues use organotypic 3D models, transcriptomic analyses, mathematical modelling and in vivo tumour data to show that single cells oscillate between two anticorrelated expression states defined by TGFBR3 and JUND. They show that this signalling circuit is controlled by the engagement of the extracellular matrix, and propose that dynamic changes in gene expression states might underlie breast tumour heterogeneity.
Del Sal and colleagues demonstrate that the YAP and TAZ effectors of the Hippo pathway are under the control of the mevalonate pathway. They show that mutant p53 and SREBP-dependent activation of mevalonate signalling activates YAP and TAZ and promotes tumour formation in mice, a growth phenotype also conserved in Drosophila.
Vale and colleagues report the distinct abilities of different tubulin isotypes and post-translational modifications to regulate different microtubule motors and their properties.
Lecuit and colleagues use Drosophila embryo cellularization as an in vivo model system, as well as in vitro reconstitution assays, to show that septin mutant embryos display defects in actin organization and that septins are able to crosslink, bundle and bend actin filaments into rings.