News & Views in 2010

Tumour suppressors of the Forkhead box O (FoxO) family are proposed to limit tumour growth through direct transcriptional regulation. Cytosolic FoxO1 can also suppress tumour growth by triggering autophagy and ultimately cell death in a transcription-independent manner.

The importin-β-like transport receptors and RanGTP govern selective transport of proteins into the nucleus. It has now been shown that importin-β2 (alternatively called transportin1) also selectively targets the motor protein Kif17 to primary cilia. In analogy to the nucleus, RanGTP in the intraciliary compartment mediates dissociation of Kif17 from its transport receptor and thereby completes import.

Adherens junctions, the sites of cadherin-dependent cell–cell adhesion, are also important for dynamic tension sensing, force transduction and signalling. Different myosin motors contribute to adherens junction assembly and versatility in distinct ways.

Innovations in live-cell microscopy and single-molecule analysis have allowed a new direct view of nuclear messenger RNA dynamics. A new study extends previous analyses of mRNA-protein intranuclear transport and links this critical step to the kinetics of moving through nuclear pore complexes. Seeing nuclear mRNA on the move will impact future work on pore translocation and nuclear organization.

The distribution of secreted morphogens in a developing organ determines its form by instructing size, shape and pattern. Pentagone has been identified as a secreted factor that controls the distribution of the morphogen Decapentaplegic (Dpp) in the Drosophila melanogaster wing.

The balance of cohesion and remodelling is essential for the integrity and morphogenesis of epithelia. This requires adhesion and transmission of actomyosin tension, both of which are mediated by E-cadherin. The finding that actomyosin tension reinforces mechanical coupling of actin to E-cadherin through α-catenin reveals similarities with integrin regulation.

CRACR2A is a newly discovered Ca²⁺-binding protein that regulates store-operated Ca²⁺ entry (SOCE). CRACR2A enhances SOCE by promoting the binding of the endoplasmic reticulum Ca²⁺ sensor STIM to Orai, a Ca²⁺ channel located in the plasma membrane. As intracellular Ca²⁺ levels rise, CRACR2A binds Ca²⁺ and triggers SOCE inactivation by dissociating from the Orai–STIM complex.

Formation of multivesicular bodies (MVBs) from endosomes or budding of enveloped virus such as HIV-I from the plasma membrane require the ESCRT (endosomal sorting complex required for transport) complexes. An in vitro reconstitution assay unambiguously identifies the function of each ESCRT complex in the sequential events of MVB morphogenesis, from cargo clustering and membrane bud formation to sequestration of cargoes in vesicles, and fission of the vesicles into the lumen of the endosome.

Instability in the structure and number of chromosomes is a trait common to cells from most epithelial cancers. A role in chromosome segregation for a pathway previously implicated in the DNA damage response reveals new connections between the tumour suppressive processes that maintain chromosome integrity.

Although all cells within a colon cancer may harbour adenomatous polyposis coli (APC) or β-catenin mutations, activation of Wnt signalling is limited to a subpopulation of cells that display cancer stem cell properties. This activation requires a co-stimulatory signal mediated by hepatocyte growth factor, which is produced by tumour-associated myofibroblasts.

Cilia drive fluid flow in development and physiology, but this requires that all cilia in a tissue orient the same way. Earlier studies indicated that both planar cell polarity (PCP) signalling and cilia-generated fluid flows could influence ciliary orientation. We now learn how asymmetric localization of PCP proteins influences the position and orientation of cilia to control the direction of flow.

The deubiquitylating enzyme Dub3 is found to have oncogenic potential by stabilizing the Cdc25A protein phosphatase, a crucial regulator of cell-cycle progression.

Cytokinesis — the final step of mitosis in which the two daughter cells separate — requires accumulation of specific proteins and lipids at the connecting bridge to ensure cleavage by abscission. Phosphatidylinositol-3-phosphate (PtdIns(3)P), an endosomal phosphoinositide, and FYVE-CENT, a PtdIns3P-binding protein, are found in the bridge, where they contribute to the mechanism of abscission.

Peroxisomes can import large multimeric protein complexes and even 9-nm gold particles decorated with peroxisome-targeting signals. They achieve these feats of protein passage using a distinctive translocon whose highly dynamic aqueous pore can expand to accommodate the increasing girths of different peroxisome receptor–cargo complexes.

Bone remodelling in vertebrates is coordinately regulated by the opposing effects of parathyroid hormone (PTH) and transforming growth factor-beta (TGF-β). PTH couples the processes of bone resorption and formation by enforcing simultaneous internalization of TGF-β type II receptor (TβRII) and PTH type 1 receptor (PTH1R), which attenuates both TGF-β and PTH signalling in vivo.

The p62 protein recognizes toxic cellular waste, which is then scavenged by a sequestration process known as self-eating or autophagy. Lack of autophagy leads to accumulation of p62, which is not good for liver cells, as it induces a cellular stress response that leads to disease.

The microRNA miR-9 is induced by Myc in breast cancer cells where it targets the major epithelial adherens junction protein, E-cadherin. This primes the cancer cells for epithelial–mesenchymal transition (EMT) and also stimulates angiogenesis in tumours.

Recent studies have revealed a prominent role of mitochondrial dysfunction in the development of one of the most common neurodegenerative disorders, Parkinson's disease. The ubiquitin ligase Parkin and the protein kinase PINK1, whose mutations are associated with Parkinson's disease, function in a pathway that links ubiquitylation with selective autophagy of damaged mitochondria.

Separation of sister chromatids at anaphase in metazoan cells requires only the cleavage of the kleisin subunit of centromeric cohesin, but efficient poleward movement of separated sisters requires the associated loss in Cdk1 activity. Activation of the anaphase-promoting complex/cyclosome ensures these events are coordinated.

Adipocytes and scar tissue form during skeletal muscle degeneration. Two new studies reveal that adipocytes and fibroblasts in skeletal muscle derive from a population of bipotent progenitors that reside within muscle, but are not derived from the muscle lineage. These progenitor cells also have a surprising role in stimulating the restoration of muscle mass during regeneration.