Reviews & Analysis

A surprising functional association between TRPM3, a mysterious member of the family of transient receptor potential (TRP) cation channels, and the sulphated version of pregnenolone, 'mother' of all steroid hormones, has been identified.

The spindle assembly checkpoint is crucial for maintaining genome integrity in dividing cells by preventing premature chromosome segregation. Degradation of the APC/C activator Cdc20 seems to be an essential and conserved mechanism to maintain this checkpoint in the presence of chromosomes that are not attached to the mitotic spindle.

Studies in Drosophila melanogaster reveal a mechanism for regulating caspases, the key executioners of the apoptotic cell-death program. An initiator caspase and its activating partner promote degradation of each other, thereby limiting the levels of the active protease complex. This negative-feedback inhibition helps to explain how cells avoid unwanted caspase activation and apoptosis.

The tumour suppressor p53 triggers either cell-cycle arrest or apoptosis. Now, arginine methylation joins a panoply of other post-translational modifications that regulate p53. PRMT5 mediates p53 methylation, which disposes the cell to arrest rather than death.

Mammalian hairs have characteristic patterns of orientation, with a predominantly rostral to caudal direction, occasional swirls and a high level of local correlation between hairs. A detailed new study demonstrates that the polarity of hairs derives from an underlying planar polarity of the basal epidermal cells from which hair follicles arise.

Trans-tail regulation is the linked post-translational modification of tails on different histones. Two important studies implicate Swd2 as the link between H2B ubiquitylation and H3 methylation. Swd2 is a component of both the SET1 methyltransferase complex and the cleavage and polyadenylation factor CPF, implicating trans-tail regulation in differentiating events at the beginning and end of genes.

The balance between proliferation and differentiation is essential not only for the generation and maintenance of tissues, but also to prevent uncontrolled cell division and tumorigenesis. The mitotic kinase Aurora A coordinates cell-cycle events and asymmetric division by regulating localization of the cell fate determinant Numb through remodelling of the conserved PAR polarity complex.

Strict control of cisternal pH in the Golgi is required for posttranslational modification and trafficking of proteins and lipids. A chloride channel to neutralize the charge of the proton pump and to keep the Golgi membrane potential near zero has finally been discovered.

The tumour suppressor VHL is known to suppress hypoxia-induced gene expression by degrading HIF family transcription factors. Evidence that VHL also targets the oncoprotein β-catenin for degradation highlights a new road to transformation by loss of VHL.

Individual neurons form specific elaborate dendritic structures that receive presynaptic information. The pattern of dendritic branching is regulated by the microtubule-associated motor protein dynein, which is responsible for the transport of essential endosomes and other organelles into the dendrites.

Stress granules and processing bodies are related mRNA-containing granules implicated in controlling mRNA translation and decay. A genomic screen identifies numerous factors affecting granule formation, including proteins involved in O-GlcNAc modifications. These results highlight the importance of post-translational modifications in translational control and mRNP granule formation.

Talin can activate integrins to bind the extracellular matrix and also connect matrix-engaged integrins to the actin cytoskeleton. New work shows that cell spreading can be dissected into three distinct phases according to their differential requirements for talin function.

The epithelial–mesenchymal transition (EMT) is a cellular transdifferentiation program that enables epithelial cancer cells to acquire traits of high-grade malignancy, notably invasive and metastatic powers. A new study indicates that it may also function early in tumour progression by preventing oncogene-induced senescence.

The self-perpetuating amyloid isoform, or prion, of the yeast translation termination factor eRF3 modulates programmed translational frameshifting that controls a regulatory circuit determining the polyamine levels in a yeast cell. But it is still unclear whether this effect is adaptive or pathological.

Even though less than 2% of the mammalian genome encodes proteins, a significant fraction can be transcribed into non-coding RNAs. An elegant study identifies a function for non-coding RNA transcription in activating neighbouring genes.

The mammalian target of rapamycin (mTOR) controls cell growth and size. Amino acids are known to activate TOR, and Rag (Ras-related GTP-binding protein) GTPases have now been found to act as their effectors.

Endothelial barrier function requires the adhesive activity of VE-cadherin and claudin-5, which are key components of adherens and tight endothelial junctions, respectively. Emerging evidence suggests that VE-cadherin controls claudin-5 expression by preventing the nuclear accumulation of FoxO1 and β-catenin, which repress the claudin-5 promoter. This indicates that a crosstalk mechanism operates between these junctional structures.

In endocrine cells, secretion can be rapidly upregulated in response to stimuli without the need for additional synthesis of transport components. A new and unexpected function of KDEL-R as a signalling receptor that senses cargo protein load in the early secretory pathway has been identified.