News & Views in 2009

MicroRNAs (miRNAs) regulate gene expression in many different organisms and cell types. In mouse embryonic stem cells, a regulatory circuit that involves let-7 and its target mLin41, which encodes an E3 ubiquitin ligase, facilitates polyubiquitylation of the miRNA effector Argonaute 2 (Ago2) and targets it for degradation.

During cell migration, actin retrograde flow is counteracted by integrin-mediated adhesion to the underlying matrix, providing traction for forward movement. But in the absence of this 'clutch' mechanism, some types of cells adapt their actin polymerization to maintain similar migration speeds.

Long-range communication between animal cells can be accomplished through thin tunnelling nanotubes. The generation of these delicate structures involves dynamic remodelling of actin and the plasma membrane. Now, some of the proteins that help to build these intercellular conduits have been identified.

Identifying therapies to slow down ageing and delay age-associated diseases is a primary goal of ageing-related research. Resveratrol and rapamycin were first found to promote longevity in yeast, and their effects were then extended to several organisms. Spermidine is a new longevity drug that can increase life span in yeast, nematodes and flies, possibly through an effect on chromatin-mediated regulation of gene expression.

The tumour suppressor Tip60 is a histone acetyltransferase implicated in transcriptional control and DNA double-strand break repair. Tip60 binds to the heterochromatic histone mark H3K9me3, triggering acetylation and activation of DNA double-strand break repair factors.

Intravital imaging demonstrates that TGF-β signalling regulates the mode of cancer cell motility. Cells with active TGF-β signalling migrate as single cells and are capable of hematogenous and lymphatic spread, whereas cells lacking TGF-β signalling invade lymphatics collectively.

To fulfil its lipid phosphatase function, PTEN must be in close proximity to the plasma membrane where its substrates reside. PTEN translocation to the plasma membrane is an active process that is mediated by the myosin-based transport machinery. MyosinV controls PTEN membrane association and thus, PTEN-mediated cell growth in neurons.

Various microbes harness the actin polymerization machinery through their surface proteins to allow intracellular motility within host cells, but other virulence factors regulate dissemination. The cortical actin tension of polarized cells may represent a physical barrier that hinders the formation of microbial protrusions during cell-to-cell spreading.

Progerin, a mutated form of lamin A, causes the premature ageing disease Hutchinson-Gilford progeria syndrome and is also involved in normal ageing. Progerin accumulation leads to distinct chromatin-related defects and the NURD complex appears to affect ageing-related chromatin defects.

Centrosome duplication is under strict control such that it occurs only once per cell cycle. New insights into the molecular mechanisms that control centrosome number come from the discovery of a role for SADB kinase in centrosome biogenesis.

Transcriptional cycling of activated glucocorticoid receptor (GR) and ultradian glucocorticoid secretion are well established processes. Ultradian hormone release is now shown to result in pulsatile gene transcription through dynamic exchange of GR with the target-gene promoter and GR cycling through the chaperone machinery.

The RNA-induced silencing complex (RISC) downregulates expression of the genes targeted by RNA-silencing pathways. But formation and turnover of the RISC complex itself is tightly regulated and requires endosomal membranes.

Aurora A, an integral mitotic kinase, is essential for microtubule dynamics of post-mitotic neurons. PKCζ activates Aurora A, which in turn phosphorylates NDEL1 to promote neurite extension. This raises the possibility that Aurora A may also be involved in establishing cell polarity and axon/dendrite elaboration in young neurons.

In Caernorhabditis elegans, homologue pairing is mediated by specialized regions near one end of each chromosome in conjunction with zinc finger (ZnF)-bearing proteins. Families of repeated sequences that are enriched within these regions have now been identified. By recruiting their cognate ZnF-bearing proteins, these regions promote pairing and synapsis.

Senescent cells alter their microenvironment by secreting a growing collection of factors, a phenomenon termed the senescence-associated secretory phenotype (SASP). Cellular senescence is often the result of nuclear DNA damage fuelling a chronic DNA damage response (DDR). Upstream elements of the DDR cascade are necessary for full blown SASP, and additional crosstalk occurs between the DDR and cytokine secretion.

Translation of localized mRNAs is an important mechanism for controlling spatially discrete cellular processes. The polarity protein Par-3 is locally translated in axons in response to factors such as NGF and netrin-1, and this increased expression is necessary for factor-stimulated axonal outgrowth.

Errors in chromosome–spindle attachments during cell division can lead to an irreversible change in chromosome number. Proper connections between chromosomes and spindle microtubules can be promoted by both chromosome-intrinsic and extrinsic mechanisms during mitosis and meiosis.

In the Notch pathway, the transmembrane ligand Delta is internalized and then re-established on the surface of signal-sending cells to allow the productive binding and activation of the Notch receptor on neighbouring cells. Arp2/3-dependent actin polymerization directs Delta trafficking through this circuit.

SDPR is a new regulator of caveolae biogenesis. SDPR overexpression results in increased caveolae size and leads to the formation of caveolae-derived tubules containing Shiga toxin. SDPR may therefore be a membrane curvature-inducing component of caveolae.

For nucleosome-encoded epigenetic information to be transmitted, an epigenetic mark requires a 'reader' for its physical recognition. CENP-N has now been identified as a reader of the centromere-specifying epigenetic mark that is generated by incorporation of the histone H3 variant CENP-A into centromeric nucleosomes.