Articles in 2013

Schiebel and colleagues use in vitro techniques and yeast genetics to study the role of GTP binding in the microtubule nucleation activity of γ-tubulin.

Wei and colleagues report that phosphorylation of Sin1 by S6K or Akt results in its dissociation from mTORC2, thus suppressing mTORC2 activity. A cancer-patient-derived Sin1 mutation that impairs this phosphorylation leads to mTORC2 hyperactivation and increased tumour formation in mice.

Hauf and colleagues modulate the amount of spindle assembly checkpoint (SAC) proteins in fission yeast, revealing that a small reduction can cause checkpoint errors. However, levels of critical proteins normally show little variation, which explains the robustness of the SAC.

Reactivation of fetal gene programs has been linked to hypertrophy of postnatal cardiomyocytes and heart disease, but so far the transcription factors responsible for this effect have not been well defined. De Windt and colleagues have found that the fetal cardiac transcription factor Hand2 is re-expressed in response to stress signalling and induces cardiac hypertrophy.

Devreotes and colleagues analyse cytoskeletal regulator and signal transduction networks and use computational simulations to provide a model for cell migration. They propose that activation of an excitable signalling network needs to engage an oscillatory cytoskeletal network to promote formation of large protrusions and cell motility.

The microcephaly protein ASPM is required for correct spindle positioning in neuroepithelial cells. Basto and colleagues demonstrate that, in addition to having a role in cell division, the fly ASPM orthologue Asp is important for the maintenance of neuroepithelium integrity by mediating myosin II apico-basal polarity.

Hedgehog (Hh) acts as a morphogen to regulate growth and cell fate specification, and several hypotheses have been proposed for its movement. Using in vivo imaging, Bischoff and colleagues find that cytonemes drive Hh movement in the wing imaginal disc epithelium and that Hh gradient establishment correlates spatially and temporally with cytoneme formation.

Adult differentiated cells can be reprogrammed to lineage-restricted proliferating neural precursors in vitro. Zhang and colleagues show that the transcription factor SOX2 is sufficient to reprogram resident astrocytes in the mouse brain to neuroblasts that can proliferate and differentiate following treatment with histone deacetylase inhibitors and differentiating factors BDNF and noggin.

The RAS-like GTPase RALB mediates cellular responses to nutrient availability or viral infection by engaging two distinct exocyst complex proteins: EXO84 to modulate autophagy and SEC5 to regulate innate immune signalling. Sablina and colleagues find that whereas ubiquitylation of RALB at K47 promotes its interaction with SEC5, the de-ubiquitylase USP33 switches RALB to the EXO84–beclin complex to promote autophagy during nutrient starvation.

ER–Golgi transport and autophagy are tightly connected. Liang and colleagues find that UVRAG binds to PtdIns(3)P to localize it to the ER, from where, under normal conditions, it regulates the transport of COPI cargo transfer to the ER and Golgi integrity, but from where, following autophagy induction, it dissociates to modulate ATG9 transfer to autophagosomes.

Quality control of misfolded proteins is thought to involve proteasome-dependent degradation or, if this fails, sequestration into inclusion bodies. Frydman and colleagues reveal the existence of endoplasmic-reticulum-associated structures, termed Q-bodies, that concentrate misfolded proteins in a chaperone-dependent manner before degradation.

How injured mitochondria are targeted for autophagic degradation is not well understood. Chu and colleagues find that pro-mitophagy stimuli induce externalization of cardiolipin to the outer mitochondrial membrane of neuronal cells, and find that this is required for binding of the autophagy protein LC3 to mitochondria and mitophagy.

Ng and colleagues show that the spliceosome-associated factor SON is essential for the maintenance of pluripotency and the survival of human embryonic stem cells. Using genome-wide RNA profiling to identify SON-regulated transcripts, they find that it modulates splicing of transcripts of pluripotency regulators such as OCT4, PRDM14, E4F1 and MED24.

Carroll and colleagues show that the atypical cadherin Fat4 derived from stromal fibroblasts cooperates with Wnt9b produced by the ureteric bud to modulate self-renewal and differentiation of kidney progenitors.

Skin stem cells are amplified in early development. Yi and colleagues found that miR-205 promotes neonatal skin stem cell expansion by directly targeting negative regulators of PI(3)K–Akt signalling to maintain proliferation.

Reactive oxygen species inhibit mTORC1 signalling, but the subcellular localization of this event has been unclear. Walker and colleagues show that the tuberous sclerosis complex (TSC) is located at the peroxisome, where it functions as a Rheb GTPase-activator protein to suppress mTORC1 and induce autophagy. They also show that disease-associated mutations in TCS2 display impaired peroxisome localization and mTORC1 repression.

Grishchuk and colleagues report that CENP-E, which is known to transport chromosomes towards the plus end of spindle microtubules, is also able to track microtubule tips bi-directionally.

In the Hippo pathway, the atypical cadherins Fat and Dachsous modulate tissue growth. Harvey and colleagues have identified two regulators of the Hippo pathway, the WD40 protein Riquiqui and the DYRK kinase Minibrain, that act downstream of Dachsous to inhibit Wts and promote Yki-dependent tissue growth.

Upstream inputs providing directional bias in cellular polarity within the plane of an epithelium (PCP) remain unclear. Mlodzik and colleagues found that the Wnt ligand Wingless and Drosophila Wnt homologue dWnt4 establish the PCP axis perpendicular to their expression domain through modulating interactions between the recognized core PCP components Frizzled and Van Gogh.

Autophagy, which is believed to be an Atg7- and Atg3-dependent process, is known to be involved in animal development. Baehrecke and colleagues show that autophagy drives the controlled degradation of the developing Drosophila midgut. Interestingly, this process is Atg7- and Atg3-independent, and instead requires the E1-activating enzyme Uba1 for programmed reduction of cell size in the midgut.