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Spindle orientation plays a pivotal role in tissue morphogenesis. An asymmetric anthrax receptor cap is revealed to promote activation of a formin to orient the spindle along the planar cell polarity (PCP) axis in zebrafish dorsal epiblast cells.
Genome sequencing and RNAi have been powerful allies in the quest to assign function to every gene. Systematic RNAi screens identify essential genes efficiently, but are less effective with pleiotropic or redundant genes. A common trick used by geneticists to overcome this problem is to screen for genetic interactors — mutations that enhance or suppress the phenotype of a starting mutation. Now, this classic approach has been combined with the versatility of RNAi to generate an expanded gene network for cell polarity.
Primordial germ cell (PGC) development in the human fetus remains relatively uncharted. A new study suggests that epigenetic reprogramming and sex differentiation in human PGCs occur asynchronously over an extended time period. This finding raises questions and implications for in vitro PGC differentiation.
This month, we launch a series of specially commissioned review and perspective articles on cancer cell biology, covering key topics and recent advances in understanding the cellular mechanisms underlying cancer.
ER tubules grow and fuse to give the ER its characteristic shape. English and Voeltz show that the small GTPase Rab10 is crucial for ER tubule growth and fusion. Rab10 localizes to the leading edge of new ER tubules with enzymes that promote phospholipid synthesis, suggesting that ER tubule growth, fusion and phospholipid synthesis might be coupled.
The mTORC1 complex promotes protein translation and cell growth, whereas mTORC2 promotes survival. The Tel2 and Tt1 proteins belong to both complexes. Bassermann and colleagues demonstrate that following growth-factor deprivation, casein kinase 2 mediates phosphorylation of Tel2 and Tt1, specifically in the mTORC1 complex, to target them for degradation by the SCFFbxo9 ubiquitin ligase. This mechanism inactivates mTORC1 and activates mTORC2 and Akt signalling to promote survival of multiple myeloma cells.
Muthuswamy and colleagues demonstrated that loss of the Par3 polarity protein cooperates with ErbB2 activity to promote cell invasion and metastasis by destabilizing E-cadherin-dependent cell–cell junctions.
Mammary gland morphogenesis involves the polarization of epithelial cells and the formation of a lumen. Akhtar and Streuli demonstrate that β1 integrin and the downstream kinase ILK at the basement membrane are required for polarization in this system, through orientation of microtubules and Golgi positioning.
Robinson and colleagues perform a human-genome-wide siRNA screen to identify regulators of clathrin-coated vesicle formation. The knockdown phenotype of one of their hits, V-ATPase, is rescued by exogenous cholesterol, revealing an intriguing link between cholesterol and clathrin-coated vesicle formation.
An intriguing intersection between the AMPK and Hippo signalling pathways provides fresh insight into how nutrient availability regulates cell growth. Tapon and colleagues show that Drosophila salt-inducible kinases (Sik2/3), members of the AMPK family, phosphorylate the Hippo pathway protein Sav to attenuate Hippo signalling and promote Yki transcriptional activity.
Accurate chromosome segregation requires that sister-chromatid cohesion is resolved first at chromosome arms in prophase and then at centromeres in metaphase. In prophase, centromeric cohesion is protected by shugoshin and protein phosphase 2A (SGO1–PP2A). Yu and colleagues show that CDK1-mediated phosphorylation of SGO1 promotes SGO1–PP2A binding to cohesin, and dephosphorylation of the cohesion-promoting component sororin to prevent cohesin removal.
Cell polarity is important for the function of many animal cells, and several aspects of its establishment are conserved across species, from worm to human. Ahringer and colleagues have performed large-scale genetic interaction screens in Caenorhabditis elegans to identify a network of polarity regulators that includes genes not previously associated with polarity, such as the nuclear pore protein NPP-2.