Volume 13 Issue 5, May 2011

This issue presents a series of specially commissioned articles that highlight exciting facets of stem cell research, including recent insights into the nature of pluripotency and how studying stem cells can increase our understanding of normal ageing and disease.

Starvation of animals or cells triggers autophagic degradation of cell contents to retrieve nutrients, but, paradoxically, mitochondria enlarge. This is now shown to result from inhibition of mitochondrial fission through PKA-mediated phosphorylation of the GTPase DRP1. Elongation of mitochondria optimizes ATP production and spares them from autophagy-mediated destruction.

Induced pluripotent stem (iPS) cells offer the possibility to generate patient-specific cell types for use in regenerative medicine. However, a long-lasting question remains: are iPS and embryonic stem cells equivalent? iPS cells retain a transcriptional memory of their origin, which is now shown to endure with passages and to correlate with defects in the re-establishment of DNA methylation. Both selective pressure and genomic environment may account for these defects.

COPII-coated vesicles drive protein export from the endoplasmic reticulum (ER), although the regulation of this event, both spatially and kinetically, remains unclear. TFG is now defined as a factor that modulates recruitment of the coat and links ER sequestration of kinases to oncogenesis.

The polarized distribution of E-cadherin observed in Drosophila embryos during epithelial cell intercalation is shown to be controlled by polarized clathrin- and dynamin-mediated endocytosis. This process depends on the activity of diaphanous and myosin II, which regulate the lateral clustering of E-cadherin.

A systematic comparison shows that differential DNA methylation accounts for some of the differences in somatic gene expression between induced pluripotent stem cells (iPSCs) and embryonic stem cells. The somatic genes that have persistent expression in iPSCs tend to be isolated from other genes that undergo silencing during reprogramming. This may explain the observed delay in recruitment of the DNA methylation machinery and in the genes being silenced.

TFG-1 is identified as a regulator of COPII coat assembly that interacts with SEC-16 to control protein exit from the endoplasmic reticulum. TFG–kinase fusion proteins have been detected in some cancers and might promote oncogenesis by prematurely phosphorylating target substrates as they exit the endoplasmic reticulum.

ARFGAP1 regulates COPI coat formation and participates in COPI-dependent trafficking. ARFGAP1 is now shown to interact with the clathrin adaptor complex AP-2 through a region distinct from its COP1-interacting domain, and to regulate transport of AP-2 cargo proteins.

Cdk5-mediated phosphorylation of endophilin B1 is shown to be required for autophagy induction in starved neurons, by promoting endophilin B1 dimerization and recruitment of the autophagy regulator UVRAG. This effect leads to neuronal loss in models of Parkinson’s disease.

How do exocytic vesicles disengage from the exocyst complex? Phosphorylation of the RalA GTPase effector Sec5, rather than RalA inactivation per se, is now shown to mediate dissociation of the Sec5–RalA complex.

Mitochondria are found to fuse at the onset of autophagy. This event, which is regulated by a cyclic AMP–PKA (protein kinase A) signalling pathway, increases ATP synthase activity to prevent starvation-induced cell death.

In meiosis, HORMAD1 promotes alignment of homologues chromosomes and formation of the synaptonemal complex and is required for efficient accumulation of checkpoint and repair proteins on unsynapsed DNA.

The plant hormone auxin promotes the degradation of inhibitors of ARF transcription factors to control plant development, but the role of auxin in patterning has been unclear. The ARF protein MONOPTEROS is shown to induce both its own expression and that of its inhibitor, with auxin acting as a threshold-specific trigger to switch this feedback system to MONOPTEROS accumulation.

In Arabidopsis thaliana, Early Flowering 4 (ELF4) is essential for maintenance of the circadian rhythm. Now three transcription factors are found that activate ELF4 during the day, but are negatively regulated at dawn to ensure cyclic ELF4 expression.

Axin negatively regulates Wnt signalling by promoting degradation of β-catenin. Poly(ADP)-ribosylation of axin induces its degradation to relieve this inhibition. The ubiquitin ligase RNF146 is now shown to recognize and ubiquitylate PARsylated axin2.

On collision, cilia and flagella swim backwards owing to the generation of mechanoreceptor potential. Transient Receptor Potential 11 is found to localize to the proximal region of Chamydomonas flagella and to mediate this mechanoperception.