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The activation of the [[alpha].sub.1]-adrenoceptor-([[alpha].sub.1]-AR) by norepinephrine results in the G-protein (Gq[alpha]) mediated increase in the phosphoinositide-specific phospholipase C (PLC) activity. The byproducts of PLC hydrolytic activity, namely, 1,2-diacylglycerol and inositol-1,4,5-trisphosphate, are important downstream signal transducers for increased protein synthesis in the cardiomyocyte and the subsequent hypertrophic response. In this article, evidence was outlined to demonstrate the role of cardiomyocyte PLC isozymes in the catecholamine-induced increase in protein synthesis by using a blocker of [[alpha].sub.1]-AR and an inhibitor of PLC. The discussion was focused on the [[alpha].sub.1]-AR-Gq[alpha]-PLC-mediated hypertrophic signalling pathway from the viewpoint that it may compliment the other [[beta].sub.1]-AR-Gs protein-adenylyl cyclase signal transduction mechanisms in the early stages of cardiac hypertrophy development, but may become more relevant at the late stage of cardiac hypertrophy. From the information provided here, it is suggested that some specific PLC isozymes may potentially serve as important targets for the attenuation of cardiac hypertrophy in the vulnerable patient population at-risk for heart failure. Key words: phospholipase C isozymes, norepinephrine, [[alpha].sub.1]-adrenoceptor, cardiomyocytes, protein synthesis, signal transduction, hypertrophic response L'activation des recepteurs [[alpha].sub.1] adrenergiques (R[[alpha].sub.1]-A) par la norepinephrine entraine une augmentation de l'activite de la phospholipase C (PLC) specifique a la phosphoinositide, mediee par la proteine G (Gq[alpha]). Les sous-produits de l'activite hydrolytique de la PLC, soit le 1,2-diacylglycerol et l'inositol-1,4,5-trisphosphate, sont d'importants transducteurs du signal en aval pour l'augmentation de la synthese proteique dans le cardiomyocyte, avec la reaction d'hypertrophie qui s'en suit. Dans cet article, nous circonscrivons les donnees pour montrer le role des isoenzymes de la PLC des cardiomyocytes dans l'augmentation de la synthese proteique engendree par les catecholamines a l'aide d'un agent bloquant les R[[alpha].sub.1]-A et d'un inhibiteur de la PLC. La discussion sera centree sur la voie de signalisation de l'hypertrophie mediee par l'axe R[[alpha].sub.1]-A-Gq[alpha]-PLC a partir de la notion qu'elle pourrait completer les autres modes d'action de transduction du signal par l'axe R[[beta].sub.1]-A-proteine Gs-adenylyl cyclase aux stades precoces de l'evolution de l'hypertrophie, mais qu'elle pourrait jouer un role encore plus important aux stades tardifs de l'hypertrophie cardiaque. A partir des renseignements apportes ici, nous laissons entendre que certaines isoenzymes specifiques de la PLC pourraient eventuellement servir de cibles de choix pour l'attenuation de l'hypertrophie cardiaque dans une population de patients vulnerables exposes a un risque accru d'insuffisance cardiaque. [Traduit par la Redaction] Mots-cles : isoenzymes de la phospholipase C, norepinephrine; recepteur [[alpha].sub.1]-adrenergique, cardiomyocytes, synthese proteique, transduction du signal, reaction d'hypertrophie, Introduction Although the sympathetic nervous system regulates cardiac function, overactivity of the sympathetic nervous system under stressful conditions is known to result in the excessive production of circulating catecholamines as [...]

Peptide-chain elongation during protein synthesis entails sequential aminoacyl-tRNA selection and translocation reactions that proceed rapidly (2-20 per second) and with a low error rate (around 10.sup.-3 to 10.sup.-5 at each step) over thousands of cycles.sup.1. The cadence and fidelity of ribosome transit through mRNA templates in discrete codon increments is a paradigm for movement in biological systems that must hold for diverse mRNA and tRNA substrates across domains of life. Here we use single-molecule fluorescence methods to guide the capture of structures of early translocation events on the bacterial ribosome. Our findings reveal that the bacterial GTPase elongation factor G specifically engages spontaneously achieved ribosome conformations while in an active, GTP-bound conformation to unlock and initiate peptidyl-tRNA translocation. These findings suggest that processes intrinsic to the pre-translocation ribosome complex can regulate the rate of protein synthesis, and that energy expenditure is used later in the translocation mechanism than previously proposed. Cryo-electron microscopy and single-molecule fluorescence methods are used to elucidate the mechanism of early translocation events on the bacterial ribosome., Author(s): Emily J. Rundlet [sup.1] [sup.2] , Mikael Holm [sup.1] , Magdalena Schacherl [sup.3] , S. Kundhavai Natchiar [sup.1] , Roger B. Altman [sup.1] , Christian M. T. Spahn [sup.3] [...]

The relevance of molecular mechanisms governing mitochondrial proteostasis to the differentiation and function of hematopoietic and immune cells is largely elusive. Through dissection of the network of proteins related to HCLS1-associated protein X-1, we defined a potentially novel functional CLPB/HAX1/(PRKD2)/HSP27 axis with critical importance for the differentiation of neutrophil granulocytes and, thus, elucidated molecular and metabolic mechanisms underlying congenital neutropenia in patients with HAX1 deficiency as well as bi- and monoallelic mutations in CLPB. As shown by stable isotope labeling by amino acids in cell culture (SILAC) proteomics, CLPB and HAX1 control the balance of mitochondrial protein synthesis and persistence crucial for proper mitochondrial function. Impaired mitochondrial protein dynamics are associated with decreased abundance of the serine-threonine kinase PRKD2 and HSP27 phosphorylated on serines 78 and 82. Cellular defects in [HAX1.sup.-/-] cells can be functionally reconstituted by HSP27. Thus, mitochondrial proteostasis emerges as a critical molecular and metabolic mechanism governing the differentiation and function of neutrophil granulocytes., Introduction Neutrophil granulocytes are critical mediators of innate immunity (1). In a highly controlled process of granulopoiesis, granulocyte-monocyte progenitors develop into mature neutrophils (2, 3). This developmental path is orchestrated [...]