Post-hatching syrinx development in the zebra finch: an analysis of androgen receptor,aromatase, estrogen receptor α and estrogen receptor β mRNAs

In zebra finches, the vocal organ (syrinx) is larger in males than in females. Specific details about the mechanisms responsible for this dimorphism are not known, but may involve sex differences in steroid hormone action early in post-hatching development. The distribution of androgen receptor (AR), aromatase (AROM), estrogen receptor (ER), and estrogen receptor (ER) mRNAs was examined at post-hatching days 3, 10 and 17. A low level of AR was equivalently expressed in the syrinx muscles of both sexes at all three ages. We detected no specific expression of AROM or ER mRNAs. In contrast, ER mRNA was detected in chondrocytes of the forming bone. The density of this expression increased with age as the chondrocytes hypertrophied, but did not differ between the sexes. Taken together, these data suggest that estrogens may act on cartilage/bone, and androgens may act on muscle fibers in early post-hatching development to influence syrinx morphology. However, the lack of a sex difference in steroid receptor mRNA expression in the syrinx suggests that, similar to the forebrain regions that control song, the interaction of androgens and estrogens with their receptors is not sufficient to induce full sexual differentiation of this organ.     

Preassembly and ligand-induced restructuring of the chains of the IFN-γ receptor complex： the roles of Jak kinases, Statl and the receptor chains

We previously demonstrated using noninvasive technologies that the interferon-gamma （IFN-γ） receptor complex is preassembled [ 1 ]. In this report we determined how the receptor complex is preassembled and how the ligand-mediated conformational changes occur. The interaction of Statl with IFN-γR1 results in a conformational change localized to IFN- γR1. Jakl but not Jak2 is required for the two chains of the IFN-γ receptor complex （IFN-γR1 and IFN-γR2） to interact; however, the presence of both Jakl and Jak2 is required to see any ligand-dependant conformational change. Two IFN- γR2 chains interact through species-specific determinants in their extracellular domains. Finally, these determinants also participate in the interaction of IFN-γR2 with IFN-γR1. These results agree with a detailed model of the IFN-γ receptor that requires the receptor chains to be pre-associated constitutively for the receptor to be active.     

Functional characteristics of the high affinity IgG receptor, FcγRI

IgG FcRs are important mediators of immunity and play a key role during Ab-based immunotherapy. Within the leukocyte IgG receptor family, only FcγRI is capable of IgG binding with high affinity. FcγRI exists as a complex of a ligand binding α-chain and an FcR γ-chain. The receptors' α-chain can, furthermore, elicit several functions independent of the ITAM-bearing FcR γ-chain. Functional implications of high-affinity IgG binding and mechanisms underlying FcR γ-chain-independent signaling remain unclear to this day. In this paper, we provide an overview of past literature on FcγRI and address the implications of recently described interactions between cytosolic proteins and the FcγRI α-chain, as well as cytokine-enhanced FcγRI immune complex binding. Furthermore, an analysis of potential polymorphisms within the FCGR1A gene is provided.     

Suppression of the androgen receptor function by quercetin through protein–protein interactions of Sp1, c-Jun, and the androgen receptor in human prostate cancer cells

We have previously reported that the increase in c-Jun expression induced by quercetin inhibited androgen receptor (AR) transactivation, and Sp1 was involved in quercetin-mediated downregulation of AR activity. Transient transfection assays in this work revealed that co-expression of c-Jun quenched Sp1-induced production of luciferase activity driven by AR promoter or three copies of Sp1 binding elements in the AR promoter. Moreover, c-Jun repressed AR-mediated luciferase activity via androgen-response elements (AREs) of the hK2 gene, while this suppression could be restored partially by cotransfection of Sp1 expression plasmid. The physical associations of c-Jun, Sp1, and AR induced by quercetin were further demonstrated by co-immunoprecipitation experiments. In addition, quercetin-mediated repression of AR expression and activity was partially reversed by blocking of JNK signaling pathway. These results suggested that c-Jun might play an important role in the suppression of AR expression and activity in the presence of quercetin, and association of a c-Jun/Sp1/AR protein complex induced by quercetin represented a novel mechanism that was involved in down-regulation of the AR function in prostate cancer cells.     

Where is the vitamin D receptor?

The vitamin D receptor (VDR) is a member of the nuclear receptor superfamily and plays a central role in the biological actions of vitamin D. VDR regulates the expression of numerous genes involved in calcium/phosphate homeostasis, cellular proliferation and differentiation, and immune response, largely in a ligand-dependent manner. To understand the global function of the vitamin D system in physiopathological processes, great effort has been devoted to the detection of VDR in various tissues and cells, many of which have been identified as vitamin D targets. This review focuses on the tissue- and cell type-specific distribution of VDR throughout the body.     

Death receptor agonist therapies for cancer,which is the right TRAIL?

The activation of cell-surface death receptors represents an attractive therapeutic strategy to promote apoptosis of tumor cells. Several investigational therapeutics that target this extrinsic pathway, including recombinant human Apo2L/TRAIL and monoclonal agonist antibodies directed against death receptors-4 (DR4) or -5 (DR5), have been evaluated in the clinic. Although Phase 1/1b studies provided encouraging preliminary results, findings from randomized Phase 2 studies failed to demonstrate significant clinical benefit. This has raised multiple questions as to why pre-clinical data were not predictive of clinical response. Results from clinical studies and insight into why current agents have failed to yield robust responses are discussed. In addition, new strategies for the development of next generation death receptor agonists are reviewed.     

Scavenger receptor,Class B,Type I provides an alternative means for β-VLDL uptake independent of the LDL receptor in tissue culture

Recent evidence suggests that scavenger receptor, class B, type I (SR-BI) plays a physiological role in VLDL metabolism. SR-BI was reported to mediate β-VLDL uptake; however, cellular details of this process are not well characterized. In the present study we show that SR-BI delivers cholesterol derived from β-VLDL to LDL receptor negative SR-BI over-expressing Chinese Hamster Ovarian cells (ldlA7-SRBI). Cell association of β-VLDL was ∼ 3 times higher after SR-BI over-expression, which was competed by β-VLDL, but only to a lesser extent by HDL and LDL. Almost all of the associated β-VLDL was located intracellularly, and therefore could not be released by a 50-fold excess of unlabeled β-VLDL. β-VLDL was degraded at a rate of 6 ng β-VLDL/mg cell protein and hour. In contrast to ldlA7 cells, β-VLDL association was competed by LDL in cells with a functional LDL receptor like CHO and HepG2 cells, indicating a strong impact of the LDL receptor in β-VLDL uptake. β-VLDL degradation was similar to ldlA7-SRBI cells. When β-VLDL uptake was followed using fluorescence microscopy, β-VLDL showed a different uptake pattern in SR-BI over-expressing cells, ldlA7-SRBI, compared to LDL receptor containing cells, CHO and HepG2.     

Synaptic mechanisms controlling receptor unit activity in the stretch receptor—Abdominal ganglionic chain system of the crayfish

Inhibitory control over activity of the receptor neuron was investigated in a preparation of the stretch receptor and abdominal ganglionic chain in crayfishes. Potentials were recorded intracellularly from receptor neurons and neurons of the abdominal ganglion, and extracellularly from the dorsal roots. IPSPs appeared in the receptor neuron in response to stimulation of that same neuron or of the abdominal ganglionic chain. The relationship between spikes at the input and output of the inhibitory neuron varied over a wide range depending on the functional state of the neuron. A linear relationship was established between the time before appearance of the IPSP and the duration of the interspike interval of the slowly adapting neuron (SAN) and also between the firing rate of this and the inhibitory neurons during recurrent inhibition. Factors influencing the length of the interspike interval of the SAN on the appearance of an IPSP in it were investigated. It is postulated that summation of potentials evoked by spikes of the SAN and also of potentials evoked by spikes of that neuron, together with local processes evidently of endogenous nature takes place in the inhibitory neuron. IPSPs were recorded from two neurons resistant to strychnine and blocked by picrotoxin on the receptor neuron. The structural and functional organization of the individual elements in the chain of recurrent inhibition and inhibition evoked by stimulation of the abdominal ganglionic chain is discussed.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 5, No. 3, pp. 323–332, May–June, 1973.     

Is receptor oligomerization causally linked to activation of the EGF receptor kinase?

Transduction of a signal from an extracellular peptide hormone to produce an intracellular response is often mediated by a cell surface receptor, which is usually a glycoprotein. The secondary intracellular signal(s) generated after hormone binding to the receptor have been intensively studied. The nature of the primary signal generated by ligand binding to the receptor is understood less well in most cases. The particular case of the epidermal growth factor (EGF) receptor is analyzed, and evidence for or against two dissimilar models of primary signal transduction is reviewed. Evidence for the most widely accepted current model is found to be unconvincing. Evidence for the other model is substantial but indirect; a direct test of this model remains to be done.     

A family of proteins related to Spätzle, the toll receptor ligand, are encoded in the Drosophila genome

The Drosophila gene Sp?tzle encodes the activating ligand for the Toll receptor. This signaling pathway is required for dorso-ventral patterning in the early embryo and an antifungal immune response in larvae and adults. The genome sequence of Drosophila shows that there are a total of eight Toll-like receptors and these may function in other aspects of embryonic development and innate immunity. Here we describe five Drosophila homologues of Sp?tzle (Spz2-6) found using an iterative searching method. All five appear to encode proteins containing neurotrophin-like cystine-knot domains. In addition, most retain a characteristic intron-exon structure shared with the prototype Sp?tzle gene. This provides evidence that the family arose by ancient gene duplication events and indicates that the gene products may represent activating ligands for corresponding Toll receptors. Expression studies show that only Spz4 is expressed strongly in larvae and adults and thus may be involved in an ancillary antifungal response mediated by Toll-5. By contrast, Spz6 shows a complex spatial and temporally regulated expression pattern in the late embryo. Thus the new Toll/Sp?tzle families of signaling molecules may have important roles in other aspects of development and immunity.     

Association of the subunits of the calcium-independent receptor of α-latrotoxin

CIRL-1 also called latrophilin 1 or CL belongs to the family of adhesion G protein-coupled receptors (GPCRs). As all members of adhesion GPSR family CIRL-1 consists of two heterologous subunits, extracellular hydrophilic p120 and heptahelical membrane protein p85. Both CIRL-1 subunits are encoded by one gene but as a result of intracellular proteolysis of precursor, mature receptor has two-subunit structure. It was also shown that a minor portion of the CIRL-1 receptor complexes dissociates, producing the soluble receptor ectodomain, and this dissociation is due to the second cleavage at the site between the site of primary proteolysis and the first transmembrane domain. Recently model of independent localization p120 and p85 on the cell surface was proposed. In this article we evaluated the amount of p120-p85 complex still presented on the cellular membrane and confirmed that on cell surface major amount of mature CIRL-1 presented as a p120-p85 subunit complex.     

Effects of ischaemia,reperfusion and α1 receptor stimulation on the inositoltrisphosphate receptor population in rat heart atria and ventricles

Binding sites specific for inositol 1,4,5-trisphosphate (InsP₃) have been demonstrated in sarcoplasmic reticulum vesicles isolated from heart muscle. Scatchard analysis of a binding isotherm indicated a high as well as a low affinity binding site [1]. In this study a comparison was made between InsP₃ binding to crude microsomal membranes prepared from rat heart atria and ventricles respectively. Results obtained showed a four-fold higher incidence of binding to atrial membranes. Furthermore, the receptor populations of the atria and ventricles behaved differently during conditions causing fluctuations in tissue InsP₃ levels, viz. ischaemia, reperfusion and ₁-adrenergic stimulation. Reperfusion, as well as phenylephrine stimulation, caused an increase in InsP₃ levels associated with down-regulation of the ventricular InsP₃ receptor population while binding to atrial binding sites was elevated. In the ventricular population this down-regulation was the result of a reduction in B_max alone with no changes in the Kd values of the high- or the low-affinity binding sites. The reason(s) for the differential response of the atrial and ventricular InsP₃ receptor populations to changes in InsP₃ levels, remains to be established.