Science signaling podcast: 21 July 2015

© 2015 American Association for the Advancement of Science. All rights Reserved. This Podcast features an interview with Cristina Murga and Rocio Vila-Bedmar, authors of a Research Article that appears in the 21 July 2015 issue of Science Signaling, about how deleting the kinase GRK2 can counteract some of the metabolic effects of a bad diet. Obesity affects many of the body's normal functions, most notably metabolism. Obesity is associated with insulin resistance and reduced glucose tolerance, which can lead to type 2 diabetes. It also promotes hepatic steatosis, the accumulation of fat in the liver. Vila-Bedmar et al. show that deleting GRK2 can prevent further weight gain and hepatic steatosis and improve glucose sensitivity in obese mice. Deleting GRK2 improved these metabolic consequences of high-fat diet-induced obesity even if the kinase was deleted after the mice had already become obese and resistant to insulin.Peer Reviewe

PhD

dissertationDorsal closure is the morphogenetic process by which the Drosophila melanogaster embryo becomes completely encased in cuticle-secreting epidermis. Epithelial cells on either side of the embryo spread dorsally and replace the amnioserosa, meeting and fusing along the dorsal midline to create a continuous epidermal sheet. Failure of this process results in embryonic lethality characterized by defects in the dorsal epidermis most often manifest as a single large hole in the dorsal cuticle. Dorsal-open group genes define two groups of molecules: those that contribute to closure as components of signaling cascades and those that act as mechanical effectors of closure. Cell shape changes are mediated by the mechanical effectors (cytoskeletal, junction and adhesion molecules) and are controlled by the Jun N-terminal Kinase (JNK) and Decapentaplegic (Dpp) signaling pathways. The JNK cascade is required for activation of the Dpp pathway, but both signals contribute to morphogenesis independently. The links between signaling events and cell shape change have not been identified. Here I describe the identification and characterization of a novel dorsal closure locus, kephalaea keph. Genetic evidence places keph in the Dpp signaling pathway. However, keph also interacts with JNK signaling components and mechanical effectors, suggesting that Keph may function in the integration of the JNK and Dpp signals or in the transmission of signaling to the mechanical effectors. The keph locus encodes a novel protein with no characterized domains or motifs that would suggest a biochemical function for the protein. I propose that Keph functions downstream of Dpp and JNK to link signaling events to morphogenesis driven by the mechanical effectors. In addition to its role in dorsal closure, Keph also functions in head involution, and identifies a requirement for Dpp signaling in this morphogenetic process

Science Signaling Podcast: 1 May 2012

This Podcast features a conversation with an author of a Research Article published in the 1 May 2012 issue of Science Signaling. Hiroshi Suga discusses the evolution of tyrosine kinases during the transition from unicellularity to multicellularity in the animal lineage. Suga and colleagues analyzed the tyrosine kinase complement of filastereans, which are unicellular organisms that are the closest relatives to the clade that includes the multicellular animals (metazoa) and the choanoflagellates, a group of free-living unicellular and colonial eukaryotes. They found that filastereans share the same basic repertoire of cytoplasmic tyrosine kinases with metazoans and choanoflagellates, but that the receptor tyrosine kinase repertoire of each group differed, implying that this class of tyrosine kinases underwent diversification in each of the lineages. These findings imply that ancestral unicellular eukaryotes used a limited set of receptor tyrosine kinases to receive information from the environment and that these receptors were recruited for use in cell-cell communication and underwent subsequent amplification and diversification in the metazoan lineage.Peer Reviewe

Science Signaling Podcast for 25 October 2016: How glucocorticoids stimulate fat

A secreted protease inhibits diet- and glucocorticoid-induced differentiation of adipocytes (Wong et al ., in 25 October 2016 issue)

Science Signaling Podcast: 5 April 2011.

International audienceThis Podcast features a conversation with the senior authors of a Research Article published in the April 5 issue of Science Signaling. Sophie Ugolini and Eric Vivier discuss their team's finding that signaling through inhibitory NK cell receptors determines the distribution of activating receptors, which, in turn, determines the responsiveness of the cells to activating stimuli. This finding suggests that inhibitory receptors can affect membrane receptor organization and hence the responsiveness of NK cells

Science Signaling Podcast for 24 January 2017: Tissue-specific regulation of L-type calcium channels.

This Podcast features an interview with Johannes Hell and Manuel Navedo, senior authors of two Research Articles that appear in the 24 January 2017 issue of Science Signaling, about tissue-specific regulation of the L-type calcium channel CaV1.2. This channel is present in many tissues, including the heart, vasculature, and brain, and allows calcium to flow into cells when it is activated. Signaling through the β-adrenergic receptor (βAR) stimulates CaV1.2 activity in heart cells and neurons to accelerate heart rate and increase neuronal excitability, respectively. Using mouse models, Qian et al found that βAR-mediated enhancement of CaV1.2 activity in the brain required phosphorylation of Ser1928, whereas βAR-mediated enhancement of CaV1.2 activity in the heart did not require phosphorylation of this residue. In a related study, Nystoriak et al demonstrated that phosphorylation of Ser1928 in arterial myocytes was required for vasoconstriction during acute hyperglycemia and in diabetic mice. These findings demonstrate tissue-specific differences in CaV1.2 regulation and suggest that it may be possible to design therapies to target this channel in specific tissues.Listen to Podcast