Volume 13 Issue 1, January 2011

Despite their potential importance as therapeutic targets, the initial events in neurodegenerative diseases are poorly understood. Emerging evidence suggests that presynaptic dysfunction might be an early event in these pathologies, and three papers now link dysregulation of SNARE protein levels and function caused by the absence of synuclein or cysteine string protein (CSP) to activity-dependent neurodegeneration.

Whether class V myosins can work as point-to-point transporters in animal cells is highly debated. Myosin-Va is now shown to function as a point-to-point transporter that pulls the endoplasmic reticulum (ER) into dendritic spines, with important consequences for dendritic development and cerebellar motor learning.

JAK2 phosphorylates H3-Y41 residues to exclude the heterochromatin factor HP1α from chromatin. JAK2 is found to be required for maintenance of mouse embryonic stem cells through its action on the Nanog promoter. A mutant form of JAK2 associated with a myeloproliferative disorder allows embryonic stem cells to self renew in absence of cytokines.

A Bicoid gradient drives patterning along the anterior–posterior axis in Drosophila embryos. Degradation of Bicoid by the F-box protein Fsd is shown to be required for the correct gradient profile of bicoid and developmental fate determination.

A chaperone complex containing CSPα, Hsc70 and SGT binds to monomeric SNAP-25 and prevents its aggregation and degradation. Loss of CSPα inhibits SNARE complex formation.

The role of actin-based motors and the mode of endoplasmic reticulum (ER) transport into spines had remained unclear. Myosin-Va is now shown to act as a point-to-point ER transporter into dendritic spines.

A complex containing the Par3/6 polarity proteins and the matrix receptor DDR1 modulates migration by downregulating cortical actomyosin contractility.

Deletion of the E3 ubiquitin ligase Wwp2 in mice is shown to induce malformations in the craniofacial regions. Wwp2 mono-ubiquitylates Goosecoid, a modification found to be essential for Goosecoid effects on the transcription of the cartilage regulatory protein Sox6.

The four transcription factors Oct4, Sox2, Klf4 and c-myc induce somatic cells to reprogramme to an early embryonic stem cell state. When expressed in somatic cells under culture conditions that are normally used for stem cells derived from mouse epiblast tissue of post-implantation embryos (EpiSCs), these factors drive reprogramming to a state that closely resembles EpiSCs, highlighting the importance of culture environment in determining the outcome of reprogramming.

In the developing mouse embryo, a region of the dorsal aorta endothelium generates haematopoietic cells, but how the switch to endothelium or haematopoiesis is controlled has been unclear. HoxA3 induces endothelial differentiation through repression of key haematopoietic transcription factors, including Runx1, and is downregulated during haematopoietic differentiation.

Apoptotic cell corpses are engulfed and removed through an evolutionarily conserved pathway. In Caenorhabditis elegans, inhibition of the Rac GAP SRGP-1 permits sick or dying cells to escape clearance by this pathway.

The Polycomb group protein EZH2 promotes trimethylation of histone H3K27 and gene silencing. Cdk1 is found to phosphorylate EZH2 to inhibit its methyltransferase activity, affecting EZH2-target genes involved in osteogenic differentiation.

The formation of subnuclear domains, such as the paraspeckles where hyperdited mRNAs are stored, is not well understood. The transcription of the paraspeckle non-coding RNA MEN ɛ/β initiates the recruitment of other components to assemble this nuclear body.

The genetic locus encompassing TSPYL5 is frequently amplified in breast cancer. TSPYL5 is now shown to repress p53 accumulation by interacting with and inhibiting the p53 de-ubiquitylating enzyme USP7.