Articles in 2011

The E3 ligase RNF8 is recruited to double-strand breaks in DNA to promote repair. Jacobs and colleagues discovered that RNF8 also goes to unprotected telomeres, where it mediates non-homologous end-joining of chromosome ends and contributes to telomere-induced genomic instability.

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.

Astral microtubules emanating from the spindle poles engage force-generating proteins such as dynein at the cell cortex to regulate spindle positioning. McAinsh and colleagues show that the microtubule-associated proteins MAP4 and CLASP1 control the interactions of astral microtubules at the cell cortex to ensure correct spindle positioning.

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.

How the unique chromatin configuration of embryonic stem cells (ESCs) integrates inputs from exogenous stimuli to maintain pluripotency remains largely unknown. The ESC-specific ATP-dependent chromatin-remodelling (esBAF) complex maintains the accessibility of the target sites of Stat3, a leukaemia inhibitory factor (LIF) signalling effector, by preventing repressive localized polycomb-mediated trimethylation of Lys 27 of histone 3 (H3K27me3).

Regulatory mechanisms to prevent centriole overduplication during the cell cycle are not completely understood. In this issue, FBXW5 is shown to control the degradation of the centriole assembly factor HsSAS-6. Moreover, the study proposes that FBXW5 is a substrate of both PLK4 and APC/C, two established regulators of centriole duplication.

Change the Equation, a non-profit group of more than 100 corporate organizations, is committed to improving the state of mathematics and science education in the US.

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.

The STAT3 transcription factor maintains pluripotency by preventing differentiation. A Brg1-containing chromatin-remodelling complex, esBAF, is shown to direct STAT3 to its targets across the pluripotent genome. Deletion of Brg1 leads to binding of the polycomb complex and subsequent silencing of LIF/STAT targets. Unexpectedly, Brg1 also helps the polycomb complex silence Hox genes thereby further contributing to pluripotency.