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The increasingly pressing problems facing postdoctoral fellows in recent years call for a re-evaluation of the position of postdocs in academia and collaboration of involved parties to bring about positive change.
Both symmetric and asymmetric divisions rely on alignment of the mitotic spindle with cues from the environment. A study now shows that mitotic spindles find their position by reading the map of forces that load-bearing retraction fibres exert on the cell body.
Microtubule-depolymerizing motor proteins regulate microtubule dynamics during chromosome segregation, but whether they can independently grip the ends of shrinking kinetochore microtubules has remained unresolved. MCAK, a member of the kinesin-13 motor protein family, is now shown to grip microtubules on its own and harness the forces of microtubule disassembly.
A combination of genetic fate mapping and imaging reveals that the distal visceral endoderm of mouse embryo arises following the migration of Lefty1-expressing primitive endoderm progenitor already present in the implanting blastocyst.
Canonical Wnt signalling and its transcriptional effector β-catenin have been implicated in embryonic stem cell (ESC) function. Self-renewal is now shown to be maintained in β-catenin-deficient mouse ESCs, whereas mesendodermal and neuronal differentiation are impaired. A β-catenin variant that cannot function in transcription but re-establishes cadherin-mediated cell-adhesion rescues these differentiation defects.
Inhibition of the repressor function of the Wnt3a effector β-catenin–TCF3 is shown to be required to maintain pluripotency in cooperation with the activating role of the second Wnt effector β-catenin–TCF1. Both Tcf3 and Tcf1 are involved in the recruitment of β-catenin to Oct4 binding sites in embryonic stem cell chromatin.
The cell division axis is determined by the position of the mitotic spindle. How geometrical cues influence spindle orientation is analysed in cells cultured on micropatterns. These experiments show that the mitotic spindle rotates to align with the forces produced by retraction fibres and suggest that forces may be transmitted through a sub-cortical actin structure.
Myosin and actin are known to reshape the plasma membrane during endocytosis. Myosin 1b regulates the actin-dependent formation of tubules at the trans-Golgi network. As such, it has a critical role in initiating post-Golgi carrier formation.
Sensory cilia assembly has been proposed to occur through the kinesin-2-driven delivery of precursors to the axoneme tip by intraflagellar transport (IFT). Microscopy analysis and mathematical modelling provide evidence that tubulin subunits are transported to their sites of incorporation into microtubules at axonemal tips by IFT.
In most eukaryotes, the centromere is defined by epigenetic marks such as the histone H3 variant CENH3/CENP-A/CID. Ectopic induction of kinetochores in Drosophila S2 cells by CID overexpression leads to kinetochore assembly specifically in silent intergenic regions bordering heterochomratin, demonstrating a role for these domains in centromere identity.
A genome-wide RNAi synthetic lethal screen unravels the role of p53 in small nucleolar RNPs (snoRNPs) through a genetic interaction with UNRIP, which has been previously shown to interact with the snoRNP chaperone SMN. p53 regulates the levels of Nolc1, which affects snoRNP stability, whereas UNRIP contributes to nuclear SMN import, revealing a synergistic requirement for both in snoRNP assembly.
The Ras GEF Ras-GRF2 is found to inhibit the activity of the Cdc42 Rho GTPase independently of its Ras-activating function. Binding of Ras-GRF2 to Cdc42 prevents its activation by Cdc42 GEFs suppressing Cdc42-mediated cell migration, invasion and transformation.
Activating mutations in the receptor tyrosine kinase Met can promote tumorigenesis. These Met mutants are now shown to undergo altered endocytic trafficking, and the retention of active Met at endosomes correlates with increased tumour formation and metastasis.
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.
Single-molecule force spectroscopy measurements show that the microtubule depolymerizing enzyme MCAK uses microtubule disassembly to generate force at both microtubule ends.
Plants possess a unique repertoire of SNARE and RAB GTPase proteins that regulate membrane trafficking events. The plant-specific RAB protein ARA6 regulates the formation of a specific SNARE complex to modulate the response to environmental cues.
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.
Budding yeast telomeres are anchored to the nuclear envelope. Siz2-mediated SUMOylation of Yku70/80 and Sir4, both known to mediate telomere anchoring, is found to promote telomere localisation at the nuclear envelope and restrain their elongation.