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41.
Godi A Di Campli A Konstantakopoulos A Di Tullio G Alessi DR Kular GS Daniele T Marra P Lucocq JM De Matteis MA 《Nature cell biology》2004,6(5):393-404
The molecular mechanisms underlying the formation of carriers trafficking from the Golgi complex to the cell surface are still ill-defined; nevertheless, the involvement of a lipid-based machinery is well established. This includes phosphatidylinositol 4-phosphate (PtdIns(4)P), the precursor for phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)). In yeast, PtdIns(4)P exerts a direct role, however, its mechanism of action and its targets in mammalian cells remain uncharacterized. We have identified two effectors of PtdIns(4)P, the four-phosphate-adaptor protein 1 and 2 (FAPP1 and FAPP2). Both proteins localize to the trans-Golgi network (TGN) on nascent carriers, and interact with PtdIns(4)P and the small GTPase ADP-ribosylation factor (ARF) through their plekstrin homology (PH) domain. Displacement or knockdown of FAPPs inhibits cargo transfer to the plasma membrane. Moreover, overexpression of FAPP-PH impairs carrier fission. Therefore, FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery that controls generation of constitutive post-Golgi carriers. 相似文献
42.
The two-faced nature of protozoa allowed us to study the relationship between cell cycle and behaviour in Euplotes crassus; the former represents one of the most typical cellular traits, the latter is one of the most significant characteristics of an organism. Dividing cells of E. crassus were isolated on a slide and recorded for 11 h: the classic ethographic parameters were calculated every 60 min. The percentage of mobile cells went from 0-100% in the first 2.5 h. This value was maintained for 6.5 h, but from 9 h the value began to drop, reaching 0% at 11 h. The relative frequency of leftward arcs was very high in the first hour, the radius and length of the arcs increased from 1-7 h; velocity showed a similar trend, peaking at 7 h. All our results showed that the behaviour of this ciliate is heavily affected by its cell-division cycle. 相似文献
43.
Appendino G Ligresti A Minassi A Daddario N Bisogno T Di Marzo V 《Bioorganic & medicinal chemistry letters》2003,13(1):43-46
Two regioisomers and 13 analogues of the putative endocannabinoid noladin ether (2-arachidonyl glyceryl ether, 2-AGE, 1) were synthesized and tested for their interaction with CB(1) receptors in rat brain membranes. The results showed that a C-20 tetra-unsaturated moiety is necessary for high affinity, and that a series of alkyl glyceryl ethers of potential occurrence in brain tissues have less affinity than 2-AGE for CB(1) receptors. 相似文献
44.
Ugolini A Fantini T Innocenti R 《Proceedings. Biological sciences / The Royal Society》2003,270(1512):279-281
The supralittoral amphipod Talitrus saltator is well known for its capacity for astronomical orientation using the sun and moon as compasses. It has also been demonstrated that the sun compass is innate in this species. In our experiments, we released inexpert (naive) young born in the laboratory into a confined environment under the full moon and in the absence of the horizontal component of the magnetic field. They were allowed to see the natural sky and the moon only at the moment of release. The young individuals were obtained in the laboratory by crossing adult individuals from the same and different populations of sandhoppers. The young from intrapopulation crosses were well oriented towards the directions corresponding to those of their parents, whereas the young from interpopulation crosses were oriented in an intermediate direction. Therefore, our experiments demonstrate in the sandhopper T. saltator that sea-land moon orientation relies on an innate chronometrically compensated mechanism. 相似文献
45.
Castelli MP Ferraro L Mocci I Carta F Carai MA Antonelli T Tanganelli S Cignarella G Gessa GL 《Journal of neurochemistry》2003,87(3):722-732
Two gamma-hydroxybutyric acid (GHB) analogues, trans-gamma-hydroxycrotonic acid (t-HCA) and gamma-(p-methoxybenzyl)-gamma-hydroxybutyric acid (NCS-435) displaced [3H]GHB from GHB receptors with the same affinity as GHB but, unlike GHB, failed to displace [3H]baclofen from GABAB receptors. The effect of the GHB analogues, GHB and baclofen, on G protein activity and hippocampal extracellular glutamate levels was compared. While GHB and baclofen stimulated 5'-O-(3-[35S]thiotriphospate) [35S]GTPgammaS binding both in cortex homogenate and cortical slices, t-HCA and NCS-435 were ineffective up to 1 mm concentration. GHB and baclofen effect was suppressed by the GABAB antagonist CGP 35348 but not by the GHB receptor antagonist NCS-382. Perfused into rat hippocampus, 500 nm and 1 mm GHB increased and decreased extracellular glutamate levels, respectively. GHB stimulation was suppressed by NCS-382, while GHB inhibition by CGP 35348. t-HCA and NCS-435 (0.1-1000 microm) locally perfused into hippocampus increased extracellular glutamate; this effect was inhibited by NCS-382 (10 microm) but not by CGP 35348 (500 microm). The results indicate that GHB-induced G protein activation and reduction of glutamate levels are GABAB-mediated effects, while the increase of glutamate levels is a GHB-mediated effect. Neither t-HCA nor NCS-435 reproduced GHB sedative/hypnotic effect in mice, confirming that this effect is GABAB-mediated. The GHB analogues constitute important tools for understanding the physiological role of endogenous GHB and its receptor. 相似文献
46.
Affaitati A Cardone L de Cristofaro T Carlucci A Ginsberg MD Varrone S Gottesman ME Avvedimento EV Feliciello A 《The Journal of biological chemistry》2003,278(6):4286-4294
A-Kinase anchor proteins (AKAPs) immobilize and concentrate protein kinase A (PKA) isoforms at specific subcellular compartments. Intracellular targeting of PKA holoenzyme elicits rapid and efficient phosphorylation of target proteins, thereby increasing sensitivity of downstream effectors to cAMP action. AKAP121 targets PKA to the cytoplasmic surface of mitochondria. Here we show that conditional expression of AKAP121 in PC12 cells selectively enhances cAMP.PKA signaling to mitochondria. AKAP121 induction stimulates PKA-dependent phosphorylation of the proapoptotic protein BAD at Ser(155), inhibits release of cytochrome c from mitochondria, and protects cells from apoptosis. An AKAP121 derivative mutant that localizes on mitochondria but does not bind PKA down-regulates PKA signaling to the mitochondria and promotes apoptosis. These findings indicate that PKA anchored by AKAP121 transduces cAMP signals to the mitochondria, and it may play an important role in mitochondrial physiology. 相似文献
47.
48.
D'Amico M Biagiotti T Fontana L Restano-Cassulini R Lasagna N Arcangeli A Wanke E Olivotto M 《Biochemical and biophysical research communications》2003,302(1):101-108
From the adrenergic SH-SY5Y human neuroblastoma clone, we isolated a subclone (21S) endowed with a glial-oriented phenotype. At difference from the parental clone, 21S cells responded to depolarizing stimuli with overshooting action potentials, whose repolarization phase was composed of an initial rapid episode, followed by a long-lasting plateau and a slow return to the resting potential (V(REST)). The action potential depolarization phase was sustained by a TTX-sensitive Na(+) current, while the first repolarizing episode was produced by the scanty delayed rectifier potassium current (I(KDR)) expressed in 21S cells. The bulk of repolarization, including the after-hyperpolarization, was sustained by the human eag related (HERG) potassium current (I(HERG)) that also governs V(REST) in 21S cells. This double role of I(HERG), together with the poor expression of I(KDRs), represents a novel finding in electrophysiology, as well as gives a clue to identify a new excitable element of the complex cellular population of neuroblastoma. 相似文献
49.
Chromosome behaviour during male meioses has been studied in two bisexual amphimictic populations of two tardigrade species, namely Richtersius coronifer and Macrobiotus richtersi (Eutardigrada, Macrobiotidae). Both bisexual populations exhibit a diploid chromosome number 2n=12 and no sex chromosomes were identified. DAPI staining and C-banding data indicate that all chromosomes of the bisexual population of R. coronifer are acrocentric. In both species, at male meiotic prophase, all six bivalent homologous chromosomes are aligned side by side along their length and show no evidence of chiasmata. However, in the oocytes of both species a chiasma is generally present in each bivalent at diplotene stage. Lack of recombination is previously unknown in tardigrades, but is a well known phenomenon in many other metazoans where it is always restricted to the heterogametic sex. In tardigrades there is no evidence of heterochromosomes, but it does not mean that in tardigrades, the heterogametic sex does not exist. The adaptive and evolutionary significance of achiasmatic meiosis is discussed. 相似文献
50.
The molecular mechanism of the proton pump activity by the respiratory chain bc1 complex is still unknown. This group has proposed since long time that protonation/deprotonation events in the apoproteins of the complex are cooperatively linked to the oxido-reduction reactions at the quinone catalytic centre. Protolytic residues in the apoproteins can thus provide proton transfer pathways between the bulk aqueons phases and the redox centre. A series of experiments has been carried out aimed at demonstrating a role of particular complex subunits in the pump process. In this paper recent results are reviewed which have evidenced a definite role of polypeptide carboxyl residues in the proton pump mechanism. In particular, experiments carried out with both the bovine and P. denitrificans purified enzymes have indicated a specific involvement of aspartic residue(s) in the Rieske Fe/S protein in the proton pump function. 相似文献