Insulin-producing cells in the brain of adult Drosophila are regulated by the serotonin 5-HT1A receptor

Insulin signaling regulates lifespan, reproduction, metabolic homeostasis, and resistance to stress in the adult organism. In Drosophila, there are seven insulin-like peptides (DILP1–7). Three of these (DILP2, 3 and 5) are produced in median neurosecretory cells of the brain, designated IPCs. Previous work has suggested that production or release of DILPs in IPCs can be regulated by a factor secreted from the fat body as well as by neuronal GABA or short neuropeptide F. There is also evidence that serotonergic neurons may regulate IPCs. Here, we investigated mechanisms by which serotonin may regulate the IPCs. We show that the IPCs in adult flies express the 5-HT_1A, but not the 5-HT_1B or 5-HT₇ receptors, and that processes of serotonergic neurons impinge on the IPC branches. Knockdown of 5-HT_1A in IPCs by targeted RNA interference (RNAi) leads to increased sensitivity to heat, prolonged recovery after cold knockdown and decreased resistance to starvation. Lipid metabolism is also affected, but no effect on growth was seen. Furthermore, we show that DILP2-immunolevels in IPCs increase after 5-HT_1A knockdown; this is accentuated by starvation. Heterozygous 5-HT_1A mutant flies display the same phenotype in all assays, as seen after targeted 5-HT_1A RNAi, and flies fed the 5-HT_1A antagonist WAY100635 display reduced lifespan at starvation. Our findings suggest that serotonin acts on brain IPCs via the 5-HT_1A receptor, thereby affecting their activity and probably insulin signaling. Thus, we have identified a second inhibitory pathway regulating IPC activity in the Drosophila brain.     

Nuclear progestin receptor in the chimpanzee sex skin

We describe for the first time the presence of a nuclear progestin receptor in the sex skin of the chimpanzee, which is possibly involved in the anti-estrogen action of progestins in the sexual swelling.     

Nuclear progestin receptor in the chimpanzee sex skin

Summary We describe for the first time the presence of a nuclear progestin receptor in the sex skin of the chimpanzee, which is possibly involved in the anti-estrogen action of progestins in the sexual swelling.This work was supported by NIH grants RR-00165 and HD-13083 to the Yerkes Primate Research Center, Emory University.     

Agonist-induced trafficking of the low-affinity formyl peptide receptor FPRL1

The formyl peptide-like receptor FPRL1 is a member of the chemoattractant subfamily of G protein- coupled receptors involved in regulating leukocyte migration in inflammation. To elucidate mechanisms underlying the internalization of ligand-bound FPRL1 and possible receptor recycling, we characterized the endocytic itinerary of FPRL1. We show that agonist-triggered internalization from the plasma membrane into intracellular compartments is prevented by perturbation of clathrin-mediated endocytosis, such as expression of the dominant-negative clathrin Hub mutant, siRNA-mediated depletion of cellular clathrin and expression of a dominant-negative mutant of the large GTPase dynamin. Internalized FPRL1 co-localized with endocytosed transferrin and the small GTPases Rab4 and Rab11 in vesicular structures most resembling recycling endosomes. Recycling of FPRL1 was significantly reduced by pretreatment with PI3-kinase inhibitors. Thus, ligand-bound FPRL1 undergoes primarily clathrin-mediated and dynamin-dependent endocytosis and the receptor recycles via a rapid PI3-kinase-sensitive route as well as pathways involving perinuclear recycling endosomes.Received 19 March 2004; received after revision 26 April 2004; accepted 12 May 2004     

Inhibition and sex specific induction of spawning by serotonergic ligands in the zebra musselDreissena polymorpha (Pallas)

Serotonin (5-hydroxytryptamine, 5-HT) stimulates spawning in the zebra mussel (Dressena polymorpha), a macrofouling European bivalve that has recently invaded North America. To develop methods of controlling zebra mussel spawning, two vertebrate serotonin antagonists, methiothepin and metergoline, known to bind with high affinity to snail 5-HT receptors, were tested for their ability to block 5-HT-induced spawning in zebra mussels. Methiothepin inhibited 5-HT-induced spawning at concentrations as low as 10^–6 M. Metergoline (10^–4 M) inhibited 5-HT-induced spawning; however, at lower concentrations (10^–8 to 10^–5 M), metergoline by itself significantly induced spawning in male, but not female zebra mussels. Metergoline (10^–5 M)-induced male spawning was inhibited by 10^–5 M methiothepin. Thus, methiothepin is the most effective inhibitor and metergoline the most powerful inducer of spawning yet tested in zebra mussels.     

Translating DRiPs: progress in understanding viral and cellular sources of MHC class I peptide ligands

It has been 15 years since we proposed the defective ribosomal product (DRiP) hypothesis to explain the rapid presentation of viral peptides by MHC class I molecules on the surface of infected cells. Here, we review the evidence for the contribution of DRiPs to antigen processing, pointing to the uncertainties regarding the physical nature of DRiPs, and emphasizing recent findings suggesting that peptide generation is a specialized process involving compartmentalized translation.     

Immunochemical differentiation between gastrin and related peptide hormones through a novel conjugation of peptides to proteins

Zusammenfassung Nachweis, dass mit Hilfe von 2,4-Dichlor-6-methoxy-1,3,5-triazin Tyrosinreste von Peptiden und Lysinreste von Proteinen miteinander verknüpft werden können. Auf dieser Basis wurde ein immunologischer Test für die Sequenz 1–13 von menschlichem Gastrin entwickelt.     

Influence of sex on radioinduced changes in longevity: comparative sensitivity of 2 strains of Drosophila melanogaster]

Two strains of Drosophila were irradiated with 25 to 75 Krads of 60Co gamma rays at a dose rate of 1 000 rad/mm, on the fourth day of imaginal life. A radiosensitivity difference between the strains was observed. However, the influence of sex was similar in the two strains, the females being more sensitive than the males.     

DNA sequence encoding the signal peptide of the lambda receptor in E. coli K 12]

A 181 base pairs DNA fragment from E. coli K 12 has been sequenced. This allows determination of the sequence of the signal peptide of the precursor for the lambda receptor, an outer membrane protein.     

Mass spectrometric determination of the amino acid sequence in peptides: Desulfurization of sulfur-containing peptides

, N- 20 - .     

Biology of the CAPA peptides in insects

CAPA peptides have been isolated from a broad range of insect species as well as an arachnid, and can be grouped into the periviscerokinin and pyrokinin peptide families. In insects, CAPA peptides are the characteristic and most abundant neuropeptides in the abdominal neurohemal system. In many species, CAPA peptides exert potent myotropic effects on different muscles such as the heart. In others, including blood-sucking insects able to transmit serious diseases, CAPA peptides have strong diuretic or anti-diuretic effects and thus are potentially of medical importance. CAPA peptides undergo cell-type-specific sorting and packaging, and are the first insect neuropeptides shown to be differentially processed. In this review, we discuss the current knowledge on the structure, distribution, receptors and physiological actions of the CAPA peptides. Received 28 April 2006; received after revision 5 June 2006; accepted 4 July 2006     

Cardioactive peptides of the CNS of the pulmonate snailLymnaea stagnalis

Summary In the pulmonate snailLymnaea stagnalis the cardioactive effects (tested on isolated auricles) of acetylcholine (ACh), 5-hydroxytryptamine (5-HT), the bivalve tetrapeptide FMRFamide, and of chromatographically separated snail brain substances have been established. Besides ACh and 5-HT, in brain extracts, small FMRFamide-like and large cardioexcitatory peptides were found.