Malaria is transmitted from vertebrate host to mosquito vector by mature sexual blood-living stages called gametocytes. Within seconds of ingestion into the mosquito bloodmeal, gametocytes undergo gametogenesis. Induction requires the simultaneous exposure to at least two stimuli in vitro: a drop in bloodmeal temperature to 5 degrees C below that of the vertebrate host, and a rise in pH from 7.4 to 8.0-8.2. In vivo the mosquito bloodmeal has a pH of between 7.5 and 7.6. It is thought that in vivo the second inducer is an unknown mosquito-derived gametocyte-activating factor. Here we show that this factor is xanthurenic acid. We also show that low concentrations of xanthurenic acid can act together with pH to induce gametogenesis in vitro. Structurally related compounds are at least ninefold less effective at inducing gametogenesis in vitro. In Drosophila mutants with lesions in the kynurenine pathway of tryptophan metabolism (of which xanthurenic acid is a side product), no alternative active compound was detected in crude insect homogenates. These data could form the basis of the rational development of new methods of interrupting the transmission of malaria using drugs or new refractory mosquito genotypes to block parasite gametogenesis.

Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito

Roles of amyloid β-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimer's disease and mild cognitive impairment

646 . . . . . . VI . Variation in composition of metal-containing granules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . VI I. Formation of metal-containing granules ( I ) Intracellular metal-containing granules . . . . . . . . 650 (2) Extracellular metal-containing granules . . . . . . . . 655 . . . . . . . . . . . . . VIII. Granule function 656 659 . . . . . . . . . . IX. General discussion and summary X. Acknowledgements . . . . . . . . . . . . 661 XI. References . . . . . . . . . . . . . . 661

The form and function of metal-containing ‘granules’ in invertebrate tissues

A vacuolar-type proton pump energizes K+/H+ antiport in an animal plasma membrane.

Microelectrode measurements of basal, apical and transepithelial potentials in the Malpighian tubules of Drosophila melanogaster were obtained under a range of conditions in order to investigate whether each of the three main second messenger systems known to act in the tubules (cyclic AMP, cyclic GMP and Ca2+) acted specifically on either cation or anion transport, or whether they activated both systems. Ion-selective microelectrode determinations of K+ concentration and pH of secreted fluid allowed the role of each signalling system to be analysed further. Stimulation with cyclic nucleotides markedly alters the potential profile across principal cells through the selective activation of an apical electrogenic V-ATPase. By contrast, manipulation of extracellular chloride levels, combined with stimulation with leucokinin, does not affect the potential profile across the principal cells, showing that chloride must pass through another route. The cell-permeant Ca2+ chelator BAPTA-AM was shown to suppress the action of leucokinins (insect peptides that induce rapid fluid secretion), but not those of cyclic AMP, the neuronally derived insect peptide cardioacceleratory peptide 2b (CAP2b) or its intracellular messenger cyclic GMP. This shows that leucokinins act through Ca2+ and not through cyclic nucleotides and that the cyclic nucleotide pathways do not co-activate the intracellular Ca2+ pathway to exert their effects. Taken together, these results show that leucokinin acts through intracellular Ca2+, independently of cyclic AMP or cyclic GMP, to raise the chloride permeability of the epithelium. By contrast, either cyclic AMP or cyclic GMP (upon CAP2b stimulation) acts on the electrogenic cation-transporting apical V-ATPase, with only a negligible effect on anion conductance and without perturbing intracellular [Ca2+]. There is thus a clear functional separation between the control pathways acting on cation and anion transport in the tubules. Given the evidence from D. melanogaster and other species that chloride does not pass through the principal cells, we speculate that these two pathways may also be physically separated within cell subtypes of the tubules.

Separate control of anion and cation transport in malpighian tubules of Drosophila Melanogaster.

Bafilomycin A1 is a potent inhibitor of urine formation by Malpighian tubules of Drosophila hydei: Is a vacuolar-type ATPase involved in ion and fluid secretion?

Two types of concretions in Drosophila Malpighian tubules as revealed by X-ray microanalysis: A study on urine formation

The Malpighian tubules of Drosophila melanogaster accumulate a great number of substances, many of which fluoresce. This paper is concerned with the identification of these substances by chromatography and their location by fluorescentmicroscopy (fig. 4, 5). It appears that they mainly belong to the following three groups: Pteridines, tryptophane and some of its metabolites, and riboflavine (tab. 1).The pattern of fluorescent substances of the eye color mutants cn, v, se, st, bw, ry, and w vary significantly. The patterns of these mutants are compared and discussed with that of the wild-type.

[Fluorescing substances from the Malpighian tubules of wild-type and various eye color mutants of Drosophila melanogaster].

Die Zellen der vier Rektalpapillen von Drosophila melanogaster sind polar gebaute, hochdifferenzierte, transportaktive Zellen mit grosflachigen Ein- und Ausfaltungen des Plasmalemms. Ihre basale und laterale Zellmembran bildet ein Netzwerk von Einfaltungen, aus dem zahlreiche Stapel von Membranpaaren hervorgehen, die mit Mitochondrien vergesellschaftet sind. Apikal besitzt die Zelle ein System von Mikroleisten, an deren Basis ebenfalls Mitochondrien akkumuliert sind (s. Abb. 9). Bei Drosophila werden nach Durchfuhrung der entsprechenden elektronenmikroskopischen Nachweise Natriumionen an den Membranen der apikalen Ausfaltungen, an den Membranen der interzellularen Stapel der Membranpaare, innerhalb deren Lumina und in den basalen und lateralen Einfaltungen gefunden. Eine bevorzugte Lokalisation von Chloridionen ist nicht vorhanden.

Armin Wessing

Papers

Bafilomycin A1 is a potent inhibitor of urine formation by Malpighian tubules of Drosophila hydei: Is a vacuolar-type ATPase involved in ion and fluid secretion?

Two types of concretions in Drosophila Malpighian tubules as revealed by X-ray microanalysis: A study on urine formation

[Fluorescing substances from the Malpighian tubules of wild-type and various eye color mutants of Drosophila melanogaster].

Elektronenmikroskopische Untersuchungen zur Struktur und Funktion der Rektalpapillen von Drosophila melanogaster

Metal-salt feeding causes alterations in concretions in Drosophila larval Malpighian tubules as revealed by X-ray microanalysis