We report the genetic, phenotypic, and biochemical analyses of Catecholamines up (Catsup), a gene that encodes a negative regulator of tyrosine hydroxylase (TH) activity. Mutations within this locus are semidominant lethals of variable penetrance that result in three broad, overlapping effective lethal phases (ELPs), indicating that the Catsup gene product is essential throughout development. Mutants from each ELP exhibit either cuticle defects or catecholamine-related abnormalities, such as melanotic salivary glands or pseudotumors. Additionally, Catsup mutants have significantly elevated TH activity that may arise from a post-translational modification of the enzyme. The hyperactivation of TH in Catsup mutants results in abnormally high levels of catecholamines, which can account for the lethality, visible phenotypes, and female sterility observed in these mutants. We propose that Catsup is a component of a novel system that downregulates TH activity, making Catsup the fourth locus found within the Dopa decarboxylase (Ddc) gene cluster that functions in catecholamine metabolism.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1460756 | PMC |
| http://dx.doi.org/10.1093/genetics/153.1.361 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The expression of Catsup in the hindgut is essential for zinc homeostasis in Drosophila melanogaster.
Insect Mol Biol
December 2024
China Light Industry Key Laboratory of Meat Microbial Control and Utilization, Hefei University of Technology, Hefei, China.
Zinc excretion is crucial for zinc homeostasis. However, the mechanism of zinc excretion has not been well characterized. Zinc homeostasis in Drosophila seems well conserved to mammals.
View Article and Find Full Text PDFZinc antagonizes iron-regulation of tyrosine hydroxylase activity and dopamine production in Drosophila melanogaster.
BMC Biol
November 2021
State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
Background: Dopamine (DA) is a neurotransmitter that plays roles in movement, cognition, attention, and reward responses, and deficient DA signaling is associated with the progression of a number of neurological diseases, such as Parkinson's disease. Due to its critical functions, DA expression levels in the brain are tightly controlled, with one important and rate-limiting step in its biosynthetic pathway being catalyzed by tyrosine hydroxylase (TH), an enzyme that uses iron ion (Fe) as a cofactor. A role for metal ions has additionally been associated with the etiology of Parkinson's disease.
View Article and Find Full Text PDFModulation of social space by dopamine in but no effect on the avoidance of the stress odorant.
Biol Lett
August 2017
Department of Biology, Western University, London, ON, Canada
Appropriate response to others is necessary for social interactions. Yet little is known about how neurotransmitters regulate attractive and repulsive social cues. Using genetic and pharmacological manipulations in , we show that dopamine is contributing the response to others in a social group, specifically, social spacing, but not the avoidance of odours released by stressed flies (dSO).
View Article and Find Full Text PDFDisruption of dopamine homeostasis has sexually dimorphic effects on senescence characteristics of Drosophila melanogaster.
Eur J Neurosci
March 2017
Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Mississippi State, MS, 39762, USA.
The neurotransmitter dopamine (DA) is known to be involved in a multitude of physiological processes. We investigated sexually dimorphic effects of disruptions in DA homeostasis and its relationship to senescence using three different Drosophila melanogaster mutants namely Catsup (Catsup ) with elevated DA levels, and pale (ple ), Punch (Pu ) with depleted DA levels. In all genotypes including controls, DA levels were significantly lower in old (45-50-day-old) flies compared with young (3-5-day-old) in both sexes.
View Article and Find Full Text PDFPerturbations in dopamine synthesis lead to discrete physiological effects and impact oxidative stress response in Drosophila.
J Insect Physiol
February 2015
Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Mississippi State, MS 39762, USA. Electronic address:
The impact of mutations in four essential genes involved in dopamine (DA) synthesis and transport on longevity, motor behavior, and resistance to oxidative stress was monitored in Drosophila melanogaster. The fly lines used for this study were: (i) a loss of function mutation in Catecholamines up (Catsup(26)), which is a negative regulator of the rate limiting enzyme for DA synthesis, (ii) a mutant for the gene pale (ple(2)) that encodes for the rate limiting enzyme tyrosine hydroxylase (TH), (iii) a mutant for the gene Punch (Pu(Z22)) that encodes guanosine triphosphate cyclohydrolase, required for TH activity, and (iv) a mutant in the vesicular monoamine transporter (VMAT(Δ14)), which is required for packaging of DA as vesicles inside DA neurons. Median lifespans of ple(2), Pu(Z22) and VMAT(Δ14) mutants were significantly decreased compared to Catsup(26) and wild type controls that did not significantly differ between each other.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!