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Accumulation of amyloid β peptide in cerebral blood vessels has been linked to brain dysfunction. SRF and myocardin transcription factors are induced by cerebral hypoxia and reduce amyloid clearance by regulating SREBP2, a transcriptional repressor that acts on the amyloid aggregate clearance factor LRP1.
Secreted frizzled-related proteins (sFRPs) were reported to antagonise Chordin processing by Sizzled, a tolloid-like metalloproteinase in Xenopus and zebrafish. Surprisingly, mammalian sFRP2 enhances the activity of tolloid-like metalloproteinases on procollagen C to modulate fibrosis associated with cardiac injury.
Incorrectly oriented chromosomes in mitosis can lead to chromosome instability and aneuploidy. The kinesins Kif2b and MCAK stimulate kinetochore-microtubule dynamics to correct mis-orientations.
The guanine nucleotide exchange factor for Ran, RCC1, dynamically binds chromatin. During apoptosis, caspase-mediated activation of Mst1 induces histone H2B phosphorylation, which immobilizes RCC1 on the chromatin, leading to a reduction in nuclear RanGTP.
Septins are cytoskeletal proteins that form a ring at the cytokinetic furrow. Now an analogous 'molecular corset' of septins is found to be required for T lymphocyte migration.
A phosphatidylserine-binding protein, MG53, is shown to participate in membrane repair. MG53 recruits vesicles to the repair site in an oxidation dependent manner and MG53-null mice develop progressive myopathy associated with defective membrane repair.
Modelling intracellular force variations at cell protrusions suggests that cell adhesion is regulated at the interface between vinculin and integrin and reveals a putative feedback between increases in tension and F-actin assembly.
The tumour suppressor p53 is subject to complex regulation and arginine methylation is now shown to provide an additional level of control. The protein arginine methyltransferase (PRMT) 5 is recruited by Strap to methylate p53 in response to DNA damage, governing the p53 response.
Ubiquitin-dependent degradation of Cdc20 by the APC/C ligase is a conserved mechanism essential for maintaining the spindle assembly checkpoint activated by unattached chromosomes.
Quantitative analysis and mathematical modelling show that cortical tension anisotropy at apical cell junctions drives cell neighbour exchanges that are responsible for elongation of Drosophila embryos. This anisotropy depends on myosin II activity.
In an unanticipated cross-talk between the steroid and insulin endocrine systems, the neuroactive steroid pregnenolone sulphate is found to activate the TRPM3 channel, leading to enhanced insulin secretion from pancreatic islets.
The chromatin mark H3K27me3 is transmitted during cell division by recruitment and binding of the PRC2 complex, which maintains the mark and leads to methylation of H3K27 on newly incorporated histones.
The large, multi-functional protein DENN/MADD is an important linker between Rab3 and the kinesin-3 motor proteins KIF1Bβ and KIF1A in the transport of synaptic vesicle precursors.
Mammalian hair follicles are aligned along the anterior–posterior axis. The planar cell polarity genes Vangl2 and Celsr1 are essential for hair follicle polarization and orientation.
A genome-wide screen reveals that the transcription factor Elf5 is epigenetically silenced in the embryonic cell lineage and that its expression is restricted to the trophoblast, where it creates a positive-feedback loop with Cdx2 and Eomes.
Regulatory loops between transcriptional activators and repressors control the circadian clock. A minimal synthetic combination of these transcription factors is sufficient to drive a robust circadian rhythm.
Two distinct steps drive COPI vesicle fission: bud-neck constriction, which is dependent on the protein BARS and COPI constituents, followed by bud-neck scission, which is dependent on phosphatidic acid.
Adhesion assembly is needed for cell migration. Horwitz and colleagues report that new adhesions assemble in the lamellipodium in a manner that is independent of myosin II but requires actin polymerization.
A siRNA screen in mammalian epithelial cells uncovers 42 genes not previously implicated in migration or adhesion. Many genes are involved in β-catenin, β1-integrin and actin signaling. Genes that accelerate migration tend to impair adhesion.