Volume 14 Issue 2, February 2012

Cancer-associated fibroblasts contribute to malignancy by expressing secreted pro-tumorigenic molecules. The microRNA miR-320 is now shown to be a crucial component of a PTEN-controlled tumour-suppressive axis in stromal fibroblasts. Loss of PTEN and miR-320 induces an oncogenic secretome that reprogrammes the tumour microenvironment to promote invasion and angiogenesis.

A protocol for efficient differentiation of human pluripotent stem cells into white and brown adipocytes now enables their detailed examination at a cellular and molecular level, facilitating the study of adipocyte dysfunction in a range of metabolic diseases including diabetes, heart disease and obesity.

Ras GTPases are tethered to cellular membranes by a farnesyl lipid that modifies a carboxy-terminal cysteine. One of the ways Ras traffics between membranes is via fluid-phase diffusion, suggesting that a cytosolic chaperone might be needed to shield the farnesyl lipid during transport. PDE6δ is now revealed to be a farnesyl-binding chaperone that facilitates the trafficking and signalling of Ras.

Asymmetric Notch signalling is important in many developmental contexts, including the division of fly sensory organ precursor (SOP) cells. Here, Notch is inactivated by Numb in the resulting pIIb daughter cell while remaining active in pIIa to direct cell fate. Using live imaging, Schweisguth and colleagues reveal that Numb and Sanpodo act together, modulating Notch trafficking to deplete it on the pIIb side of the SOP cytokinetic furrow.

Several specialized cell types assemble hundreds of motile cilia to accomplish their function. Kintner and colleagues identify the coiled-coil protein multicilin as an essential regulator of multicilia formation in Xenopus skin and the mammalian kidney. Their data indicate that multicilin activates the transcription of genes required for multicilia formation, including the transcription factor Foxj1.

Bastiaens and colleagues find that PDEδ can solubilize Ras family small GTPases, resulting in their release from cellular membranes. This concentrates Ras proteins at specific subcellular locations, which promotes their eventual association with the plasma membrane and potentiates Ras-mediated signal transduction.

Ostrowski and colleagues identify a tumour-suppressive pathway in the tumour stroma. They show that PTEN loss in stromal fibroblasts downregulates miR-320, leading to the upregulation of the ETS2 transcription factor and the induction of a secretome that promotes tumour growth, invasion and angiogenesis.

Cyclin B is targeted for proteasome-mediated degradation by the E3 ligase APC/C, which is thought to generate polyubiquitin chains for the degradation of mitotic substrates. King and colleagues now demonstrate in Xenopus laevis extracts that multiple monoubiquitylation events are sufficient to target cyclin B1 for degradation.

Damaged mitochondria can be removed by mitophagy, but how this organelle is recognized by the autophagy machinery is unclear. Chen and colleagues show that FUNDC1, an integral mitochondrial outer membrane protein, interacts with light chain 3 (LC3) and is essential for hypoxia-induced mitophagy.

Wnt signalling regulates development and differentiation through both canonical and non-canonical pathways. Rudnicki and colleagues find that Wnt7a–Fzd7 activates Gα_s to promote Akt/mTOR pathway activation, and show that this non-canonical Wnt signalling pathway elicits myofibre hypertrophy in vivo.

Endoplasmic reticulum (ER) stress and activation of the unfolded protein response inhibits de novo protein translation and activates CHOP. However, the long-term induction of these pathways in response to prolonged ER stress would be detrimental. Tabas and colleagues now reveal a mechanism through which Toll-like receptor signalling suppresses CHOP activation and promotes protein translation, thus allowing cells to adapt to persistent ER stress.

Oxygen levels regulate the stability of the transcription factor HIF-1 through the action of prolyl hydroxylases and the VHL ubiquitin ligase. Sharp and colleagues now identify a protein complex in which the Ajuba LIM-domain protein LIMD1 brings together prolyl hydroxylases and VHL to ensure efficient degradation of HIF-1.

Cowan and colleagues have developed a method to efficiently differentiate human pluripotent stem cells into functional white or brown adipocytes, through the transient expression of PPARG2 alone or in combination with CEBP and PRDM16. The programmed cells are able to give rise to ectopic fat pads with white or brown adipose tissue characteristics.