Different beta-subunits determine G-protein interaction with transmembrane receptors.

Regulatory GTP-binding proteins (G proteins) are membrane-attached heterotrimers (alpha, beta, gamma) that mediate cellular responses to a wide variety of extracellular stimuli. They undergo a cycle of guanine-nucleotide exchange and GTP hydrolysis, during which they dissociate into alpha-subunit and beta gamma complex. The roles of G-protein alpha-subunits in these processes and for the specificity of signal transduction are largely established; the beta- and gamma-subunits are essential for receptor-induced G-protein activation and seem to be less diverse and less specific. Although the complementary DNAs for several beta-subunits have been cloned, isolated subunits have only been studied as beta gamma complexes. Functional differences have been ascribed to the gamma-subunit on the basis of extensive sequence similarity among beta-subunits and apparent heterogeneity in gamma-subunit sequences. Beta gamma complexes can interact directly or indirectly with different effectors. They seem to be interchangeable in their interaction with pertussis toxin-sensitive alpha-subunits, so we tested this by microinjecting antisense oligonucleotides into nuclei of a rat pituitary cell line to suppress the synthesis of individual beta-subunits selectively. Here we show that two out of four subtypes of beta-subunits tested (beta 1 and beta 3) are selectively involved in the signal transduction cascades from muscarinic M4 (ref. 4) and somatostatin receptors, respectively, to voltage-dependent Ca2+ channels.     

The variety of thermal conduction resulting from segmented degree of heat source body and its bearing on temperature change

The differences of thermal conduction and its temperature-varying track of the heat source body at various structural environments have been studied. Hypothetically , geologic heat source body is cut successively into several segregative bodies with a fixed cubage . With the segmented number increasing , the conductive surface area of heat source body begins to get larger, which separately is similar to the heat geologic body in different tectonic zones that has a various enclosed coefficient . Finite-element simulation result shows that the thermal conduction speed of spreading from the heat source body to its wall rock is slow→higher→ highest, when heat source bodies are situated respectively at compressive, shear and tensile deformation zones, corresponding rates of their temperature drop are low→ higher→ highest . Research indicates that the temperature ' s dropping rate of heat source body has an inverse relationship with enclosed coefficient η for different structural zones . This result can explain the tectono-physicochemical reason of magmatite evolution and its. difference .     

Signalling via caveolin: involvement in the cross-talk between phosphoinositolglycans and insulin

In recent years, a number of cross-talk systems have been identified which feed into the insulin signalling cascade at the level of insulin receptor substrate (IRS) tyrosine phosphorylation, e.g., receptor and non-receptor tyrosine kinases and G-protein-coupled receptors. At the molecular level, a number of negative modulator and feedback systems somehow interacting with the beta-subunit (catecholamine-, phorbolester-, or tumor necrosis factor-alpha-induced serine/threonine phosphorylation, carboxy-terminal trimming by a thiol-dependent protease, association of inhibitory/regulatory proteins such as RAD, PC1, PED, alpha2-HS-glycoprotein) have been identified as candidate mechanisms for the impairment of insulin receptor function by elevations in the activity and/or amount of the corresponding modification enzymes/inhibitors. Both decreased responsiveness and sensitivity of the insulin receptor beta-subunit for insulin-induced tyrosine autophosphorylation have been demonstrated in several cellular and animal models of metabolic insulin resistance as well as in the adipose tissue and skeletal muscle of diabetic patients and obese Pima Indians compared to non-obese subjects. Therefore, induction of the insulin signalling cascade by bypassing the defective insulin receptor kinase may be useful for the therapy of non-insulin dependent diabetes mellitus. During the past two decades, phosphoinositolglycans (PIGs) of various origin have been demonstrated to exert potent insulin-mimetic metabolic effects upon incubation with cultured or isolated muscle and adipose cells. However, it remained to be elucidated whether these compounds actually manage to trigger insulin signalling and if so at which level of hierarchy within the signalling cascade the site of interference is located. Recent studies using isolated rat adipocytes and chemically synthesized PIG compounds point to IRS1/3 tyrosine phosphorylation by p59Lyn kinase as the site of cross-talk, the negative regulation of which by interaction with caveolin is apparently abrogated by PIG. This putative mechanism is thus compatible with the recently formulated caveolin signalling hypothesis, the supporting data for which are reviewed here. Though we have not obtained experimental evidence for the involvement of PIG in physiological insulin action, the potential cross-talk between insulin and PIG signalling, including the caveolae/detergent-insoluble glycolipid-enriched rafts as the compartments where the corresponding signalling components are concentrated, thus represent novel targets for signal transduction therapy.     

Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia

Autosomal dominant hereditary spastic paraplegia (AD-HSP) is a genetically heterogeneous neurodegenerative disorder characterized by progressive spasticity of the lower limbs. Among the four loci causing AD-HSP identified so far, the SPG4 locus at chromosome 2p2-1p22 has been shown to account for 40-50% of all AD-HSP families. Using a positional cloning strategy based on obtaining sequence of the entire SPG4 interval, we identified a candidate gene encoding a new member of the AAA protein family, which we named spastin. Sequence analysis of this gene in seven SPG4-linked pedigrees revealed several DNA modifications, including missense, nonsense and splice-site mutations. Both SPG4 and its mouse orthologue were shown to be expressed early and ubiquitously in fetal and adult tissues. The sequence homologies and putative subcellular localization of spastin suggest that this ATPase is involved in the assembly or function of nuclear protein complexes.     

Structure and electrical characteristics of Nb-doped SrTiO3 substrates

Strontium titanate (SrTiO3) has been widely used as substrates for growing perovskite oxides thin films be- cause SrTiO3 is chemically and compositionally stable, and has small lattice mismatch with many perovskite oxides[1―3]. It is known that SrTiO3 it…     

High frequency of unequal recombination in pseudoautosomal region shown by proviral insertion in transgenic mouse

The mammalian X and Y chromosomes, in contrast to the autosomes, pair during male meiosis only near the telomeres. Alleles localized in this region can undergo reciprocal exchange during meiosis. Because such sequences do not show strict sex-linked inheritance, they have been termed pseudoautosomal. In man, several DNA sequences have been described which show pseudoautosomal transmission and which are localized in the pairing region at the ends of the short arms of both the X and Y chromosomes (refs 6-9, and D. Page, unpublished results). We now show that the transgenic mouse strain, Mov-15, contains a single Moloney murine leukaemia virus (M-MuLV) genome in its germline, and genetic evidence indicates that the provirus is integrated into the pseudoautosomal region of the sex chromosome. Proviral copies are lost or gained in 7% of male meioses in this strain, and mouse sequences flanking the provirus are tandemly repeated and highly variable. We conclude that unequal recombination events occur with high frequency in the pairing region, possibly because of the presence of repeated sequences.     

On the relative position of the centromere of chromosome 3 inDrosophila melanogaster

Zusammenfassung HomozygoteDrosophila-melanogaster-Weibchen, genetisch markiert mit scarlet (st), Kinked (Ki) und pink peach (P^p) wurden bestrahlt, um Compound-3-Chromosomen herzustellen. Es wurden ausschliesslich st/st- und P^p Ki/Ki(?) P^p-Compoundchromosomen gefunden. Dies zeigt, dass das Zentromer links der Markierung Kinked liegt.

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This work was supported by Schweizerischer Nationalfonds zur Förderung der wissenschaftlichen Forschung.     

Transverse stimulation of a single node of ranvier by middle-frequency sinusoidal current bursts

Zusammenfassung Einzelne markhaltige Nervenfasern vonRana esculenta wurden mit Mittelfrequenz-Impulsen (20 kHz) quer durchströmt (Mittelfrequenz-Querreizung), Die Lage der Reizelektroden bezüglich eines Schnürrings wurde variiert, und die zugehörigen Reizschwellen wurden bestimmt. Die Simulierung der Experimente mit einem Modell zeigte, dass wirkliche Querreizung einer Nervenfaser im Bereich eines Schnürrings möglich ist, wobei für einen Schwellenreiz eine Feldstärke von 50 ± 16.5 V/cm (Scheitel zu Scheitel) notwendig ist.     

Circadian rhythm of progesterone secretion during pseudogestation in the rat

Résumé Par des canulations toutes les 6 heures chez des rattes le 7ème jour de la pseudogestation nous avons pu mettre en évidence un pic de progestérone entre 09.00 et 11.00. Sur la base de nos résultats (progestérone, 20 -OH-progestérone, poids des ovaires et corps jaune) et de la publication deFreeman etNeill ³ nous discutons le rôle de la LTH comme régulation possible de ce phénomène.

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Acknowledgements. The authors wish to express their appreciation to Dr.L. Schenkel-Hulliger for her helpful advice during this project.