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[
Cell,
2014]
The hexosamine biosynthetic pathway (HBP) generates metabolites for protein N- and O-glycosylation. Wang et al. and Denzel et al. report a hitherto unknown link between the HBP and stress in the endoplasmic reticulum. These studies establish the HBP as a critical component of the cellular machinery of protein homeostasis.
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[
Cell Metab,
2005]
Stress-activated kinases control metabolism by antagonizing the early steps of insulin signal transduction. Two papers now demonstrate that Jnk, the prototypical stress-activated kinase, controls life span in Drosophila and C. elegans by promoting phosphorylation of the forkhead protein FoxO (Oh et al., 2005; Wang et al., 2005). The findings provide yet another mechanism by which metabolic and stress responses are integrated via phosphorylation of FoxO proteins.
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[
Curr Biol,
2011]
Recent work on a Caenorhabditis elegans transmembrane ATPase reveals a central role for the aminophospholipid phosphatidylethanolamine in the production of a class of extracellular vesicles.
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[
Nat Cell Biol,
2011]
Aurora A kinase is a key regulator of cell division, whose functions were attributed to its ability to phosphorylate diverse substrates. Aurora A is now shown to have a kinase-independent role in the regulation of chromatin-mediated microtubule assembly.
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[
Elife,
2015]
Chromosome separation is regulated by a cycle that involves a protein undergoing an unusual topological conversion.
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[
Curr Biol,
2015]
As a microtubule-organizing center, the centrosome undergoes a dramatic increase in size - via expansion of the pericentriolar material - during mitosis. Recent work reveals shared assembly properties of a protein scaffold that facilitates and supports this expansion, a process critical to spindle assembly.
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[
Cell,
2014]
Li et al. demonstrate that a single interneuron can regulate analog- and digital-like behaviors guided by two different postsynaptic neurons. Releasing a single neurotransmitter onto downstream neurons that express receptors with distinct biophysical properties enables a small set of neurons to direct a range of functional responses.
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[
Nat Chem Biol,
2009]
Screening a library of expressed cyclic peptides identified clones that reverse the cytotoxicity of alpha-synuclein in yeast and Caenorhabditis elegans. The results suggest a new approach for intervention in Parkinson's disease, and perhaps a druggable target.
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[
Genetics,
2014]
Ca(2+)/calmodulin-dependent Kinase II (CaMKII) is a calcium-regulated serine threonine kinase whose functions include regulation of synaptic activity (Coultrap and Bayer 2012). A postsynaptic role for CaMKII in triggering long-lasting changes in synaptic activity at some synapses has been established, although the relevant downstream targets remain to be defined (Nicoll and Roche 2013). A presynaptic role for CaMKII in regulating synaptic activity is less clear with evidence for CaMKII either increasing or decreasing release of neurotransmitter from synaptic vesicles (SVs) (Wang 2008). In this issue Hoover et al. (2014) further expand upon the role of CaMKII in presynaptic cells by demonstrating a role in regulating another form of neuronal signaling, that of dense core vesicles (DCVs), whose contents can include neuropeptides and insulin-related peptides, as well as other neuromodulators such as serotonin and dopamine (Michael et al. 2006). Intriguingly, Hoover et al. (2014) demonstrate that active CaMKII is required cell autonomously to prevent premature release of DCVs after they bud from the Golgi in the soma and before they are trafficked to their release sites in the axon. This role of CaMKII requires it to have kinase activity as well as an activating calcium signal released from internal ER stores via the ryanodine receptor. Not only does this represent a novel function for CaMKII but also it offers new insights into how DCVs are regulated. Compared to SVs we know much less about how DCVs are trafficked, docked, and primed for release. This is despite the fact that neuropeptides are major regulators of human brain function, including mood, anxiety, and social interactions (Garrison et al. 2012; Kormos and Gaszner 2013; Walker and Mcglone 2013). This is supported by studies showing mutations in genes for DCV regulators or cargoes are associated with human mental disorders (Sadakata and Furuichi 2009; Alldredge 2010; Quinn 2013; Quinn et al. 2013). We lack even a basic understanding of DCV function, such as, are there defined DCV docking sites and, if so, how are DCVs delivered to these release sites? These results from Hoover et al. (2014) promise to be a starting point in answering some of these questions.
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[
Curr Biol,
2017]
A landmark study has revealed that an interleukin-17-like signaling system modulates a neural circuit that controls the aggregation behavior of nematodes.