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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.
Increased visceral adipose tissue has been associated with metabolic dysfunction but the origin of the progenitors that give rise to this tissue, and whether they are the same as the progenitors contributing to the protective subcutaneous adipose tissue, was unclear. Hastie and colleagues have found that Wt1-positive mesothelial cells contribute to visceral adipocytes.
Burridge and colleagues demonstrate that isolated nuclei respond to force by increasing their stiffness, and that this mechanical adaptation is mediated by emerin phosphorylation.
Hebrok and colleagues use mouse models to demonstrate that loss of the chromatin modifier Brg1 cooperates with oncogenic KRas to form lesions resembling intraductal papillary mucinous neoplasia that progress to pancreatic adenocarcinoma.
Groth and colleagues identify proteins associated with newly synthesized DNA — isolated by nascent chromatin capture — as well as proteins associated with mature DNA, and find factors not previously linked to replication or nascent chromatin.
How sensory neurons integrate mechanical signals during touch sensation has remained unclear. Using a combination of laser axotomy and FRET imaging to measure force across single cells and molecules, Goodman and colleagues show that the neuronal spectrin cytoskeleton transduces touch sensation in C. elegans.
Silberzan and colleagues demonstrate that local RhoA activity and mechanical forces control the formation of 'migration fingers', cell protrusions involved in the leader-cell-driven collective migration of epithelial cell monolayers.
Screaton and colleagues delineate a pathway involving the AMPK-related Sik2 kinase using mouse models. They show that Sik2-mediated phosphorylation and subsequent degradation of CDK5R1 (p35) by PJA2 is needed for glucose-induced insulin secretion and β-cell functional compensation in models of hyperglycemia and obesity.
Wang, Yang and colleagues delineate a Snail-β-catenin-miR-146a signalling axis that directs a switch from asymmetric to symmetric cell division, resulting in colorectal cancer stem cell expansion.
Ma and colleagues report that in E-cadherin-deficient basal-like breast cancer cells, α-catenin acts as a tumour suppressor by interacting with and stabilizing IκBα, leading to inhibition of NF-κB signalling.
Hair follicle stem cells (HFSCs) regenerate hair in response to Wnt signalling. Fuchs and colleagues use a genome-wide survey to discover that Wnt effectors TCF3, TCF4 and Groucho (TLE) coordinately repress Wnt target genes. They find that although β-catenin is dispensable for HSFC viability and proliferation, it is essential to relieve this repression to initiate hair follicle fate during the hair regeneration cycle.
Mutations in PINK1 cause early-onset Parkinson’s disease. Martins and colleagues find that the expression levels of genes involved in nucleotide metabolism are upregulated in a Drosophila pink1 mutant, and that this affects neuronal mitochondrial DNA synthesis. They find that enhancing nucleotide synthesis through genetics or pharmacological approaches rescues mitochondrial defects associated with PINK1 mutations.
Meiotic chromosome movement is needed for homologue pairing and synapsis. Watanabe and colleagues identify TERB1 as a protein needed for telomere mobility and attachment to the nuclear envelope, and for telomere enrichment of meiotic cohesin.
Yap and colleagues demonstrate that E-cadherin-based cell–cell junctions exhibit distinct patterns of apical and lateral contractility. They show that N-WASP-dependent stabilization of F-actin mediates increased apical junctional tension, and that modulation of intra-junctional tension differences can promote extrusion of cells from monolayers.
N6-methyladenosine (m6A) is an abundant internal modification of messenger RNA (mRNA) that has been reported recently in thousands of mammalian mRNAs and long non-coding RNAs (lncRNAs). Zhao and colleagues identify two methyltransferases responsible for this modification in mammalian cells, and demonstrate that they are required for embryonic stem cell self-renewal maintenance through an effect of the modification on the degradation of developmental regulator transcripts.