Cascades of multisite phosphorylation control Sic1 destruction at the onset of S phase

Multisite phosphorylation of proteins has been proposed to transform a graded protein kinase signal into an ultrasensitive switch-like response. Although many multiphosphorylated targets have been identified, the dynamics and sequence of individual phosphorylation events within the multisite phosphorylation process have never been thoroughly studied. In Saccharomyces cerevisiae, the initiation of S phase is thought to be governed by complexes of Cdk1 and Cln cyclins that phosphorylate six or more sites on the Clb5-Cdk1 inhibitor Sic1, directing it to SCF-mediated destruction. The resulting Sic1-free Clb5-Cdk1 complex triggers S phase. Here, we demonstrate that Sic1 destruction depends on a more complex process in which both Cln2-Cdk1 and Clb5-Cdk1 act in processive multiphosphorylation cascades leading to the phosphorylation of a small number of specific phosphodegrons. The routes of these phosphorylation cascades are shaped by precisely oriented docking interactions mediated by cyclin-specific docking motifs in Sic1 and by Cks1, the phospho-adaptor subunit of Cdk1. Our results indicate that Clb5-Cdk1-dependent phosphorylation generates positive feedback that is required for switch-like Sic1 destruction. Our evidence for a docking network within clusters of phosphorylation sites uncovers a new level of complexity in Cdk1-dependent regulation of cell cycle transitions, and has general implications for the regulation of cellular processes by multisite phosphorylation.     

UCP2 mediates ghrelin's action on NPY/AgRP neurons by lowering free radicals

The gut-derived hormone ghrelin exerts its effect on the brain by regulating neuronal activity. Ghrelin-induced feeding behaviour is controlled by arcuate nucleus neurons that co-express neuropeptide Y and agouti-related protein (NPY/AgRP neurons). However, the intracellular mechanisms triggered by ghrelin to alter NPY/AgRP neuronal activity are poorly understood. Here we show that ghrelin initiates robust changes in hypothalamic mitochondrial respiration in mice that are dependent on uncoupling protein 2 (UCP2). Activation of this mitochondrial mechanism is critical for ghrelin-induced mitochondrial proliferation and electric activation of NPY/AgRP neurons, for ghrelin-triggered synaptic plasticity of pro-opiomelanocortin-expressing neurons, and for ghrelin-induced food intake. The UCP2-dependent action of ghrelin on NPY/AgRP neurons is driven by a hypothalamic fatty acid oxidation pathway involving AMPK, CPT1 and free radicals that are scavenged by UCP2. These results reveal a signalling modality connecting mitochondria-mediated effects of G-protein-coupled receptors on neuronal function and associated behaviour.     

Observations on body mass of prairie dogs in urban habitat

The black-tailed prairie dog is an important component of prairie and steppe ecosystems. Currently many prairie dog colonies are fragmented by, or adjacent to, urban development, but little is known about what effects urbanization may have on these animals. I compare body weights and sex ratios of prairie dogs in isolated urban habitat in Denver, Colorado, to published data for black-tailed prairie dogs at the same time of year. Prairie dogs in this study had summer weights similar to those reported in the literature, although males apparently gained weight earlier in the year, and observed sex ratios were not significantly different from 1:1. Although prairie dogs in urban areas face numerous threats, my study provides no evidence that urban forage is limited enough to result in decreased body mass or skewed sex ratios of urban prairie dogs.     

Seismology: speed and size of the Sumatra earthquake

Our seismological results reveal that Indonesia's devastating Sumatra-Andaman earthquake on 26 December 2004 was 2.5 times larger than initial reports suggested--second only to the 1960 Chilean earthquake in recorded magnitude. They indicate that it slowly released its energy by slip along a 1,200-km fault, generating a long rupture that contributed to the subsequent tsunami. Now that the entire rupture zone has slipped, the strain accumulated from the subduction of the Indian plate beneath the Burma microplate has been released, and there is no immediate danger of a similar tsunami being generated on this part of the plate boundary, although large earthquakes on segments to the south still present a threat.