Articles in 2010

Cells sense and respond to physical stresses through mechanotransduction, a process that converts mechanical stimuli into biochemical signals. The bending of primary cilia has now been shown to modulate TOR signalling to negatively regulate cell size.

Changes in chromatin structure are a conserved hallmark of ageing, and the mechanism driving these changes, as well as their functional significance, are heavily investigated. Loss of core histones is now observed in aged cells and may contribute to this phenomenon. Histone loss is coupled to cell division and seems to be triggered by telomeric DNA damage.

The contribution and order of polarity complexes and vesicular trafficking events during lumen formation remains obscure. Now, lumenogenesis in MDCK cell cysts is shown to require a Rab11a–Rabin8–Rab8a network that recruits Sec15A and Cdc42 and that promotes apical exocytosis by enlisting the Par complex and Sec8–Sec10 to an early apical membrane initiation site.

Epithelial cell transcytosis of polymeric IgA by its receptor requires polarized membrane trafficking. A signalling cascade involving the tyrosine kinase YES, EGFR, ERK and the Rab11 effector FIP5 is now shown to regulate this process.

Protein S-nitrosylation is thought to be mediated primarily by nitric oxide synthases. S-nitrosylated GAPDH is now shown to function within signal transduction cascades as a nuclear nitrosylase. Along with other recent demonstrations of regulated protein–protein transnitrosylation, these findings point to a new mechanism of signal transduction with transformative implications for nitric oxide biology and redox signalling.

The Rickettsia protein Sca2 was previously implicated in actin ‘comet tail’ formation and bacterial cell motility. Sca2 is now found to possess formin-like properties and assembles long, unbranched actin filaments.

The mTOR pathway is a well-known regulator of cell size, and deregulation of mTOR has been observed in cilia-related diseases. Cilia modulate cell size by restricting LKB-1-mediated activation of AMPK to the basal body, which subsequently affects mTOR signalling.

Endothelial cells form a vascular niche that supports haematopoietic stem cell function. Akt activation in endothelial cells upregulates angiocrine factors to promote long-term haematopoietic stem cell repopulation capacity while co-activation of Akt and MAPK shift the balance towards maintenance and differentiation of their progenitors.

The activity of myriad nuclear proteins is regulated by S-nitrosylation, but a nuclear nitrosylase has remained elusive. GAPDH is now shown to be nitrosylated in the cytoplasm, which promotes its import into the nucleus, where it then transnitrosylates nuclear proteins.

The methyltransferase PR-Set7 catalyses the methylation of Histone H4 on Lys 20. This methylation mark is now found to correlate with replication-origin licensing. Expression of a non-degradable PR-Set7 mutant leads to retention of this mark and repeated DNA replication at origins.

The iron binding protein melanotransferrin (MTf) is found to localize to Drosophila septate junctions. During epithelial maturation, the assembly of septate junctions depends on endocytosis and recycling of iron-bound MTf.

Fish retinal regeneration starts with the dedifferentiation of glia cells into progenitors. Following injury, the proneural transcription factor, Ascl1a, upregulates the pluripotency factor Lin-28, which in turn prevents let-7 microRNA-mediated inhibition of regeneration-associated genes.

In interphase plant cells, microtubule nucleation occurs at the cell cortex. By examining the localization and dynamics of γ-tubulin nucleating complexes in Arabidopsis, the microtubule-severing protein katanin is shown to be involved in the release of daughter microtubules.

The SUMO E3 ligase PIAS3 is shown to promote Rac1 SUMOylation. This modification stimulates Rac1 activity and regulates its ability to drive lamellipodium formation.

The Polycomb group protein EZH2 promotes trimethylation of histone H3K27 and gene silencing. Cdk1 and Cdk2 are found to phosphorylate EZH2 and to positively regulate EZH2-mediated effects on global gene silencing, proliferation and migration.

Polarized-membrane trafficking supports the delivery of polarity proteins to discrete plasma-membrane domains, although the interplay between trafficking and polarity pathways is not fully understood. The small GTPases Rab8 and Rab11a direct the apical localization and activation of Cdc42 and Par3, which is essential for lumen formation.

Transcriptional noise has an important role in generating diversity in cellular populations that are seemingly identical. As this noise stems from the inherent stochasticity of gene expression, it has been unclear whether it is directly controlled. Dig1, a regulator of the budding yeast mating pathway, is now shown to prevent transcriptional noise by regulating the spatial organization of downstream gene targets.