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Kirchhausen and colleagues show that actin is required for clathrin-mediated endocytosis at membranes under tension—such as apical surfaces of polarized cells. Actin engages with Hip1R bound to clathrin light chain to complete the deformation of a clathrin-coated pit into an endocytic vesicle.
E2F is known to regulate the cell cycle, but Fajas and colleagues now show that E2F acts as a switch to allow cells to adapt to stressful metabolic conditions. Under basal conditions, E2F promotes cell-cycle progression and represses transcription of genes required for mitochondrial oxidative metabolism; however, this repression is alleviated on energy starvation.
Srivastava and colleagues find that membrane-bound Notch associates with and negatively regulates active β-catenin in embryonic stem cells, cardiac progenitors and colon cancer cells. This ligand-independent effect of Notch requires the endocytic adaptor protein Numb and targeting of β-catenin to lysosomes.
ten Berge and colleagues show that Wnt signalling is required for self-renewal of embryonic stem cells through inhibition of their differentiation into epiblast stem cells. Together, Wnt and LIF signalling can support derivation and self-renewal of embryonic stem cells.
T-box transcription factor Eomes acts during gastrulation to promote mesoderm migration and specification of the definitive endoderm. Robertson and colleagues report a further role for Eomes in directing the specification of the cardiac lineage through activation of Mesp1 upstream of the cardiac transcriptional machinery at the gastrulation stage.
Mitotic mitochondrial fission requires CDK1-mediated phosphorylation of DRP1. The Aurora A substrate RALA is found to concentrate DRP1 and RALBP1 at mitochondria to promote DRP1 phosphorylation and fission.
VCP (also called p97) recognizes and interacts with ubiquitylated cargo molecules that are destined for proteasomal degradation. Meyer and colleagues show that VCP, together with its cofactor UBXD1, sorts ubiquitylated caveolin-1 to the endolysosome system. Mutations in VCP that are associated with human degenerative diseases lack this ability.
Fork-head transcription factors are required for the maintenance of somatic stem cells. FOXO1 is now found to directly control the expression of pluripotency regulators in human embryonic stem cells, with a FOXO1 orthologue performing a similar function in mouse embryonic stem cells.
Although thousands of new neurons are generated during adult life, only a few survive, and the dying neurons are removed by phagocytosis. Ravichadran and colleagues find that in mice a specific class of neuronal progenitor cells expressing doublecortin is responsible for a significant proportion of the phagocytic activity within the neurogenic zones, through activation of the ELMO1–Rac pathway. Disruption of this process impairs neurogenesis.
Spatial organization of distinct cell populations drives organ formation. Batlle and colleagues find that ephrin signalling negatively regulates cell–cell adhesion by inducing E-cadherin shedding through the metalloprotease ADAM10 in intestinal cells so as to compartmentalize the crypt stem cell niche.
Cardiac fate choices in Ciona intestinalis depend on the CDC42-mediated formation of invasive protrusions that probe for inductive signals in the environment.
During brain development, pyramidal neurons migrate from the ventricular zone to reach their final destination in the cortex. In vivo depletion experiments shows that lamellipodin, through an effect on serum response factor, determines the neuronal migration mode in the developing cortex.
In plants, cell growth is dependent on modifications of the cell wall. In root hairs, cell wall synthesis during tip growth is found to be mediated by the activity of cellulose synthase (CESA)-like protein CSLD3, which is present in the polarized plasma membrane.
While separase is implicated in centrosome disjunction as well as in chromosome separation, its precise role at the centrosome has been uncertain. The proteolytic activity of separase is demonstrated to induce centriole disengagement through cleavage of cohesin.
PRDM16 is known to promote the differentiation of myoblastic progenitors to brown adipocytes. The miR-193b/365 microRNAs are shown to be induced by PRDM16 and promote brown fat differentiation, as well as block myogenesis.
Hsu and colleagues show that COPI-coated buds are a common progenitor for both vesicles and tubules. The choice between these two carriers is mediated by the opposing activities of the acyltransferase LPAAT-γ and the phospholipase cPLA2-α.
The PLK4 kinase and centrosomal protein HsSAS-6 both regulate centrosome duplication. PLK4 negatively controls an FBXW5-containing ubiquitin ligase, which targets SAS-6 for destruction to restrict centrosome re-duplication.
The PtdIns(4,5)P2 5-phosphatase OCRL, mutated in Lowe syndrome, is implicated in trafficking and associates with Rab GTPases. OCRL function is now extended to cytokinesis, where it controls abscission of the intercellular bridge downstream of Rab35 through the local reduction of both PtdIns(4,5)P2 levels and actin accumulation.
The self-renewal of mouse embryonic stem cells is enhanced by inhibiting glycogen synthase kinase-3 (Gsk3). β-catenin is now found to be necessary for this effect through its interaction with Tcf3 to abrogate its repressive action for the expression of genes from the core pluripotency network.
Willin and Par3 synergistically recruit aPKC to cell junctions, thus promoting aPKC-mediated phosphorylation of ROCK. This event inhibits ROCK junctional localization and apical constriction to maintain epithelial cell morphology.