ABSTRACT
The role of cyclin-dependent kinases (CDKs) that are ubiquitously expressed in the adult nervous system remains unclear. Cdk12 is enriched in terminally differentiated neurons where its conical role in the cell cycle progression is redundant. We find that in adult neurons Cdk12 acts a negative regulator of actin formation, mitochondrial dynamics and neuronal physiology. Cdk12 maintains the size of the axon at sites proximal to the cell body through the transcription of homeostatic enzymes in the 1-carbon by folate pathway which utilize the amino acid homocysteine. Loss of Cdk12 leads to elevated homocysteine and in turn leads to uncontrolled F-actin formation and axonal swelling. Actin remodeling further induces Drp1-dependent fission of mitochondria and the breakdown of axon-soma filtration barrier allowing soma restricted cargos to enter the axon. We demonstrate that Cdk12 is also an essential gene for long-term neuronal survival and loss of this gene causes age-dependent neurodegeneration. Hyperhomocysteinemia, actin changes, and mitochondrial fragmentation are associated with several neurodegenerative conditions such as Alzheimer's disease and we provide a candidate molecular pathway to link together such pathological events.
ABSTRACT
We recently identified from the Drosophila genome database a large family of G protein-coupled receptor genes, the Gr genes, and predicted that they encode taste receptors on the basis of their structure and specificity of expression. The expression of Gr genes in gustatory neurons has subsequently been confirmed and 56 family members have been reported. Here we provide functional evidence that one Gr gene, Gr5a, encodes a taste receptor required for response to the sugar trehalose. In two different mutants that carry deletions in Gr5a, electrophysiological and behavioral responses to trehalose were diminished but the response to sucrose was unaffected. Transgenic rescue experiments showed that Gr5a confers response to trehalose. The results correlate a particular taste ligand with a Gr receptor and indicate a role for G protein-mediated signaling in the transduction of sweet taste in Drosophila.
Subject(s)
Drosophila/physiology , GTP-Binding Proteins/genetics , Mutation/physiology , Neurons, Afferent/physiology , Receptors, Cell Surface/genetics , Taste/physiology , Trehalose/pharmacology , Action Potentials/drug effects , Action Potentials/physiology , Animals , Animals, Genetically Modified/genetics , Base Sequence/physiology , Behavior, Animal/drug effects , Behavior, Animal/physiology , Codon/genetics , Dose-Response Relationship, Drug , Drosophila/cytology , Food, Formulated , GTP-Binding Proteins/drug effects , GTP-Binding Proteins/metabolism , Gene Deletion , Gene Expression Regulation/physiology , Genetic Linkage/physiology , Male , Neurons, Afferent/drug effects , Phenotype , Protein Biosynthesis/physiology , Receptors, Cell Surface/drug effects , Receptors, Cell Surface/metabolism , Sucrose/pharmacology , Taste/drug effects , Trehalose/genetics , Trehalose/metabolism , X Chromosome/geneticsABSTRACT
The diurnal tsetse Glossina morsitans morsitans bites especially in early morning and late afternoon; around midday feeding is at a low. In laboratory apparatus that measures the amount of locomotion under constant conditions over the photophase, the flies display a similar patterning of activity levels. The profile of daily rhythms for G. morsitans reported in the literature includes a number of motor and sensory motor systems that fluctuate cophasically. Lacking is a study on the patterning of the senses' response levels. In this paper we present the first instance of a daily modulation in the sense of smell. We stimulated the antennae with concentration series of host-derived odours and measured the spiking rate of cells at different times during the photophase. The concentration-response curves suggest that the sensitivity of antennal olfactory cells flows in parallel with the other daily rhythms. This was also reflected in electroantennograms (EAGs). The electroantennography was extended to G. fuscipes fuscipes, whose level of spontaneous locomotor activity--instead of following a U-shaped pattern--rises gradually over the photophase. Again, the EAGs appeared to parallel the species' locomotor activity. What we believe happens is that the organism tones down the sensitivity of its odour receptors during periods of anticipated inactivity for reasons of economy.
Subject(s)
Circadian Rhythm , Taste/physiology , Tsetse Flies/physiology , Animals , Electrophysiology , Female , Male , Motor ActivityABSTRACT
Trapping tsetse flies belonging to thepalpalis group still relies totally upon luring by visual cues even though odor-baited trapping is used effectively against themorsitans-group species. Forty-three percent of the antennal olfactory cells ofGlossina f. fuscipes, a member of thepalpalis group, respond to 1-octen-3-ol. For this species we report a structure-activity relationship between 1-octen-3-ol analogs, in which carbon chain length and the configuration of the hydroxyl and π-bond moieties are varied, and biological activity. Although the optimum chain length for all cells sensitive to 1-octen-3-ol is eight and most cells give lower responses when the hydroxyl function is omitted, there is a clear division into two groups. One group is diverse and represents cells that appear indifferent to the presence or position of the π bond; many will respond to such disparate structures as acetone and 3-methylphenol as well as to 1-octen-3-ol. In the other group, the structural requirements for the stimulus are more stringent; the cells appear to be specifically tuned to 1-octen-3-ol. Their thresholds are three orders of magnitude lower than those of the former group. The existence of two clusters points to a functional division in the olfactory sense. We suggest that the latter low-threshold group is involved in host detection from a distance while the former diverse group is involved in host discrimination at close range. Trap harvests with 1-octen-3-ol as a bait may have been disappointing because the appropriate mixture for generating a landing response on the traps is still lacking.
