Plant acids modulate chemosensory responses in Manduca sexta larvae

Abstract.The effects of three plant acids on the gustatory response of Manduca sexta larvae were examined. Two different categories of response were recorded in the styloconic sensilla of different individuals in the presence of salt: the gustatory response to salt was reduced especially at the lower pHs; the deterrent cell fired particularly at the lower pHs. In some individuals neither response was seen except at the lowest pHs. Additional experiments indicated that the effect was due to pH and not to specific effects of any of the acids. Ascorbic acid was tested with the nutrient carbohydrates glucose and inositol, and was found consistently to reduce the gustatory responses to these compounds. The data indicate that plant acids at natural concentrations could influence food acceptability.     

Insect chemosensory responses: a chemical legacy hypothesis

Abstract. 1. Changes in the chemosensory responses and physiological host tolerance of phytophagous insects and parasitoids may result in new host associations. This paper considers the origin of those changes in ecological and evolutionary time.
2. The chemical legacy hypothesis postulates that effects of larval chemosensory environment on adult chemosensory responsiveness depend not (or not only) on persistent neural changes ('memory'), but on traces of chemical cues, inside or outside the insect's body, which influence adult behaviour, perhaps particularly during a 'sensitive period' associated with adult emergence or hatching of the egg.
3. Chemical cues bequeathed by earlier stages may affect adults or larvae by reducing peripheral sensitivity. Depending on the form of the dose–response curve, this change could decrease aversion or increase a positive response to a previously deterrent stimulus.
4. Attention is drawn to a possible link between this behavioural induction and the induction of detoxification enzymes. This link might be of practical importance if exposure to host allelochemicals were to influence insects' responses to insecticides, and vice versa.
5. An influence on the chemosensory responsiveness of an individual by chemical cues derived from its parents would be hard to distinguish from a genetic effect.
6. Some testable postulates of the chemical legacy hypothesis are identified.     

Carotid body chemosensory responses in mice deficient of TASK channels

Background K⁺ channels of the TASK family are believed to participate in sensory transduction by chemoreceptor (glomus) cells of the carotid body (CB). However, studies on the systemic CB-mediated ventilatory response to hypoxia and hypercapnia in TASK1- and/or TASK3-deficient mice have yielded conflicting results. We have characterized the glomus cell phenotype of TASK-null mice and studied the responses of individual cells to hypoxia and other chemical stimuli. CB morphology and glomus cell size were normal in wild-type as well as in TASK1^−/− or double TASK1/3^−/− mice. Patch-clamped TASK1/3-null glomus cells had significantly higher membrane resistance and less hyperpolarized resting potential than their wild-type counterpart. These electrical parameters were practically normal in TASK1^−/− cells. Sensitivity of background currents to changes of extracellular pH was drastically diminished in TASK1/3-null cells. In contrast with these observations, responsiveness to hypoxia or hypercapnia of either TASK1^−/− or double TASK1/3^−/− cells, as estimated by the amperometric measurement of catecholamine release, was apparently normal. TASK1/3 knockout cells showed an enhanced secretory rate in basal (normoxic) conditions compatible with their increased excitability. Responsiveness to hypoxia of TASK1/3-null cells was maintained after pharmacological blockade of maxi-K⁺ channels. These data in the TASK-null mouse model indicate that TASK3 channels contribute to the background K⁺ current in glomus cells and to their sensitivity to external pH. They also suggest that, although TASK1 channels might be dispensable for O₂/CO₂ sensing in mouse CB cells, TASK3 channels (or TASK1/3 heteromers) could mediate hypoxic depolarization of normal glomus cells. The ability of TASK1/3^−/− glomus cells to maintain a powerful response to hypoxia even after blockade of maxi-K⁺ channels, suggests the existence of multiple sensor and/or effector mechanisms, which could confer upon the cells a high adaptability to maintain their chemosensory function.     

Roles of septins in the mammalian cytokinesis machinery

Septins comprise a eukaryotic guanine nucleotide binding protein subfamily which form filamentous heteropolymer complexes. Although mechanism of cytokinesis is diverged by species and tissues, loss of septin function results in the multinuclear phenotype in many organisms. Hence septin filaments beneath the cleavage furrow are hypothesized as a structural basis to ensure completion of cytokinesis. However, molecular mechanisms of septin assembly, disassembly and function have been elusive despite the potential importance of this ubiquitous cytoskeletal system. Meanwhile, growing evidence suggests that mammalian septins functionally or physically interact with diverse molecules such as actin, actin-binding proteins, proteins of membrane fusion machinery, Cdc42 adapter proteins, a ubiquitin-protein ligase, and phosphoinositides. Careful integration of these data may provide insights into the mechanism of mammalian septin organization and functions in cytokinesis.     

Strong links between genomic and anatomical diversity in both mammalian olfactory chemosensory systems

Mammalian olfaction comprises two chemosensory systems: the odorant-detecting main olfactory system (MOS) and the pheromone-detecting vomeronasal system (VNS). Mammals are diverse in their anatomical and genomic emphases on olfactory chemosensation, including the loss or reduction of these systems in some orders. Despite qualitative evidence linking the genomic evolution of the olfactory systems to specific functions and phenotypes, little work has quantitatively tested whether the genomic aspects of the mammalian olfactory chemosensory systems are correlated to anatomical diversity. We show that the genomic and anatomical variation in these systems is tightly linked in both the VNS and the MOS, though the signature of selection is different in each system. Specifically, the MOS appears to vary based on absolute organ and gene family size while the VNS appears to vary according to the relative proportion of functional genes and relative anatomical size and complexity. Furthermore, there is little evidence that these two systems are evolving in a linked fashion. The relationships between genomic and anatomical diversity strongly support a role for natural selection in shaping both the anatomical and genomic evolution of the olfactory chemosensory systems in mammals.     

LUSH odorant-binding protein mediates chemosensory responses to alcohols in Drosophila melanogaster.

The molecular mechanisms mediating chemosensory discrimination in insects are unknown. Using the enhancer trapping approach, we identified a new Drosophila mutant, lush, with odorant-specific defects in olfactory behavior. lush mutant flies are abnormally attracted to high concentrations of ethanol, propanol, and butanol but have normal chemosensory responses to other odorants. We show that wild-type flies have an active olfactory avoidance mechanism to prevent attraction to concentrated alcohol, and this response is defective in lush mutants. This suggests that the defective olfactory behavior associated with the lush mutation may result from a specific defect in chemoavoidance. lush mutants have a 3-kb deletion that produces a null allele of a new member of the invertebrate odorant-binding protein family, LUSH. LUSH is normally expressed exclusively in a subset of trichoid chemosensory sensilla located on the ventral-lateral surface of the third antennal segment. LUSH is secreted from nonneuronal support cells into the sensillum lymph that bathes the olfactory neurons within these sensilla. Reintroduction of a cloned wild-type copy of lush into the mutant background completely restores wild-type olfactory behavior, demonstrating that this odorant-binding protein is required in a subset of sensilla for normal chemosensory behavior to a subset of odorants. These findings provide direct evidence that odorant-binding proteins are required for normal chemosensory behavior in Drosophila and may partially determine the chemical specificity of olfactory neurons in vivo.     

Roles of O-linked oligosaccharides in immune responses

Many functional glycoproteins are expressed on the lymphocyte cell surface. Some of them carry O-linked oligosaccharides (O-glycans), which are conjugated through serine or threonine residues. During various biological processes, including T-cell activation, a tetrasaccharide on the T-cell surface is dramatically converted to a branched hexasaccharide, called core2 O-glycan. The same structural change in O-glycans is also found on the lymphocytes from patients with immunodeficiency conditions such as Wiskott-Aldrich syndrome and AIDS. Several studies revealing the roles of core2 O-glycans in immune responses show that this is a biologically significant change. In particular, core2 O-glycans expressed on the cell surface reduce cell-cell interactions, thereby regulating immune responses. Furthermore, core2 O-glycan is a key backbone structure in forming selectin ligands. Thus, O-linked oligosaccharides, in particular those containing core2 branches, play vital roles in immune responses and may play dual roles in certain situations. This review will summarize the results obtained from various studies investigating the roles of O-glycans in immunological processes. BioEssays 23:46-53, 2001.     

The Drosophila larva as a model for studying chemosensation and chemosensory learning: a review

Understanding the relationship between brain and behavior is the fundamental challenge in neuroscience. We focus on chemosensation and chemosensory learning in larval Drosophila and review what is known about its molecular and cellular bases. Detailed analyses suggest that the larval olfactory system, albeit much reduced in cell number, shares the basic architecture, both in terms of receptor gene expression and neuronal circuitry, of its adult counterpart as well as of mammals. With respect to the gustatory system, less is known in particular with respect to processing of gustatory information in the central nervous system, leaving generalizations premature. On the behavioral level, a learning paradigm for the association of odors with food reinforcement has been introduced. Capitalizing on the knowledge of the chemosensory pathways, we review the first steps to reveal the genetic and cellular bases of olfactory learning in larval Drosophila. We argue that the simplicity of the larval chemosensory system, combined with the experimental accessibility of Drosophila on the genetic, electrophysiological, cellular, and behavioral level, makes this system suitable for an integrated understanding of chemosensation and chemosensory learning.     

The chemosensory responses of young cichlid fish to parents and predators

The chemosensory responses of the fry of the Midas cichlid, Cichlasoma citrinellum (Pisces: Cichlidae), were tested in a Y-maze during their first 11 days of free-swimming. Fry preferred all conspecific females to blank water but did not distinguish between their own mother, another mother or a non-parental, adult female. Fry preferred females to males. Similar results were obtained for males. Fry preferred their siblings and (unrelated) juveniles to blank water. However, while they failed to show a preference between siblings and their mother, they preferred their mother to juveniles. Fry were able to any of three heterospecifics (C. managuense, C. nigrofasciatum and the allopatric Sarotherodon mossambicus). The chemosensory responses demonstrated in the Y-maze are hypothesized to aid the fry in staying near the centre of the guarded territory and away from predators, particularly under murky or nocturnal conditions.     

Roles of F-box proteins in plant hormone responses

The F-box protein is an important component of the E3 ubiquitin ligase Skpl-Cullin-F-box protein complex. It binds specific substrates for ubiquitin-mediated proteolysis. The F-box proteins contain a signature F-box motif at their amino-terminus and some protein-protein interaction motifs at their carboxyterminus, such as Trp-Asp repeats or leucine rich repeats. Many F-box proteins have been identified to be involved in plant hormone response as receptors or important medial components. These breakthrough findings shed light on our current understanding of the structure and function of the various F-box proteins, their related plant hormone signaling pathways, and their roles in regulating plant development.     

Role of the carotid bodies in chemosensory ventilatory responses in the anesthetized mouse.

We examined the effects of carotid body denervation on ventilatory responses to normoxia (21% O2 in N2 for 240 s), hypoxic hypoxia (10 and 15% O2 in N2 for 90 and 120 s, respectively), and hyperoxic hypercapnia (5% CO2 in O2 for 240 s) in the spontaneously breathing urethane-anesthetized mouse. Respiratory measurements were made with a whole body, single-chamber plethysmograph before and after cutting both carotid sinus nerves. Baseline measurements in air showed that carotid body denervation was accompanied by lower minute ventilation with a reduction in respiratory frequency. On the basis of measurements with an open-circuit system, no significant differences in O2 consumption or CO2 production before and after chemodenervation were found. During both levels of hypoxia, animals with intact sinus nerves had increased respiratory frequency, tidal volume, and minute ventilation; however, after chemodenervation, animals experienced a drop in respiratory frequency and ventilatory depression. Tidal volume responses during 15% hypoxia were similar before and after carotid body denervation; during 10% hypoxia in chemodenervated animals, there was a sudden increase in tidal volume with an increase in the rate of inspiration, suggesting that gasping occurred. During hyperoxic hypercapnia, ventilatory responses were lower with a smaller tidal volume after chemodenervation than before. We conclude that the carotid bodies are essential for maintaining ventilation during eupnea, hypoxia, and hypercapnia in the anesthetized mouse.     

Roles of Pofut1 and O-fucose in mammalian Notch signaling

Mammalian Notch receptors contain 29-36 epidermal growth factor (EGF)-like repeats that may be modified by protein O-fucosyltransferase 1 (Pofut1), an essential component of the canonical Notch signaling pathway. The Drosophila orthologue Ofut1 is proposed to function as both a chaperone required for stable cell surface expression of Notch and a protein O-fucosyltransferase. Here we investigate these dual roles of Pofut1 in relation to endogenous Notch receptors of Chinese hamster ovary and murine embryonic stem (ES) cells. We show that fucosylation-deficient Lec13 Chinese hamster ovary cells have wild type levels of Pofut1 and cell surface Notch receptors. Nevertheless, they have reduced binding of Notch ligands and low levels of Delta1- and Jagged1-induced Notch signaling. Exogenous fucose but not galactose rescues both ligand binding and Notch signaling. Murine ES cells lacking Pofut1 also have wild type levels of cell surface Notch receptors. However, Pofut1-/- ES cells do not bind Notch ligands or exhibit Notch signaling. Although overexpression of fucosyltransferase-defective Pofut1 R245A in Pofut1-/- cells partially rescues ligand binding and Notch signaling, this effect is not specific. The same rescue is achieved by an unrelated, inactive, endoplasmic reticulum glucosidase. Therefore, mammalian Notch receptors require Pofut1 for the generation of optimally functional Notch receptors, but, in contrast to Drosophila, Pofut1 is not required for stable cell surface expression of Notch. Importantly, we also show that, under certain circumstances, mammalian Notch receptors are capable of signaling in the absence of Pofut1 and O-fucose.     

Roles for Dnmt3b in mammalian development: a mouse model for the ICF syndrome

ICF (Immunodeficiency, Centromeric instability and Facial anomalies) syndrome is a rare autosomal recessive disease caused by mutations in the DNA methyltransferase gene DNMT3B. To investigate the function of Dnmt3b in mouse development and to create animal models for ICF syndrome, we have generated three mutant alleles of Dnmt3b in mice: one carrying a deletion of the catalytic domain (null allele) and two carrying ICF-like missense mutations in the catalytic domain. The Dnmt3b null allele results in embryonic lethality from E14.5 to E16.5 with multiple tissue defects, including liver hypotrophy, ventricular septal defect and haemorrhage. By contrast, mice homozygous for the ICF mutations develop to term and some survive to adulthood. These mice show phenotypes that are reminiscent of ICF patients, including hypomethylation of repetitive sequences, low body weight, distinct cranial facial anomalies and T cell death by apoptosis. These results indicate that Dnmt3b plays an essential role at different stages of mouse development, and that ICF missense mutations cause partial loss of function. These mutant mice will be useful for further elucidation of the pathogenic and molecular mechanisms underlying ICF syndrome.     

Roles of organizer factors and BMP antagonism in mammalian forebrain establishment

A critical question in mammalian development is how the forebrain is established. In amphibians, bone morphogenetic protein (BMP) antagonism emanating from the gastrula organizer is key. Roles of BMP antagonism and the organizer in mammals remain unclear. Anterior visceral endoderm (AVE) promotes early mouse head development, but its function is controversial. Here, we explore the timing and regulation of forebrain establishment in the mouse. Forebrain specification requires tissue interaction through the late streak stage of gastrulation. Foxa2(-/-) embryos lack both the organizer and its BMP antagonists, yet about 25% show weak forebrain gene expression. A similar percentage shows ectopic AVE gene expression distally. The distal VE may thus be a source of forebrain promoting signals in these embryos. In wild-type ectoderm explants, AVE promoted forebrain specification, while anterior mesendoderm provided maintenance signals. Embryological and molecular data suggest that the AVE is a source of active BMP antagonism in vivo. In prespecification ectoderm explants, exogenous BMP antagonists triggered forebrain gene expression and inhibited posterior gene expression. Conversely, BMP inhibited forebrain gene expression, an effect that could be antagonized by anterior mesendoderm, and promoted expression of some posterior genes. These results lead to a model in which BMP antagonism supplied by exogenous tissues promotes forebrain establishment and maintenance in the murine ectoderm.     

A novel mechanism for chemosensory transduction in insects

Commentary to:

Sato K, Pellegrino M, Nakagawa T, Nakagawa T, Vosshall LB, Touhara K. Insect olfactory receptors are heteromeric ligand-gated ion channels. Nature 2008; 452:1002-6.

and

Wicher D, Schäfer R, Bauernfeind R, Stensmyr MC, Feller R, Heinemann SH, Hansson BS. Drosophila odorant receptors are both ligand-gated and cyclic nucleotide-activated cation channels. Nature 2008; 452: 1007-11.