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      Dopamine Dynamics and Signaling in Drosophila: An Overview of Genes, Drugs and Behavioral Paradigms

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          Abstract

          Changes in dopamine (DA) signaling have been implicated in a number of human neurologic and psychiatric disorders. Similarly, defects in DA signaling in the fruit fly, Drosophila melanogaster, have also been associated with several behavioral defects. As most genes involved in DA synthesis, transport, secretion, and signaling are conserved between species, Drosophila is a powerful genetic model organism to study the regulation of DA signaling in vivo. In this review, we will provide an overview of the genes and drugs that regulate DA biology in Drosophila. Furthermore, we will discuss the behavioral paradigms that are regulated by DA signaling in flies. By analyzing the genes and neuronal circuits that govern such behaviors using sophisticated genetic, pharmacologic, electrophysiologic, and imaging approaches in Drosophila, we will likely gain a better understanding about how this neuromodulator regulates motor tasks and cognition in humans.

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          Most cited references101

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          Complexity of dopamine metabolism

          Parkinson’s disease (PD) coincides with a dramatic loss of dopaminergic neurons within the substantia nigra. A key player in the loss of dopaminergic neurons is oxidative stress. Dopamine (DA) metabolism itself is strongly linked to oxidative stress as its degradation generates reactive oxygen species (ROS) and DA oxidation can lead to endogenous neurotoxins whereas some DA derivatives show antioxidative effects. Therefore, DA metabolism is of special importance for neuronal redox-homeostasis and viability. In this review we highlight different aspects of dopamine metabolism in the context of PD and neurodegeneration. Since most reviews focus only on single aspects of the DA system, we will give a broader overview by looking at DA biosynthesis, sequestration, degradation and oxidation chemistry at the metabolic level, as well as at the transcriptional, translational and posttranslational regulation of all enzymes involved. This is followed by a short overview of cellular models currently used in PD research. Finally, we will address the topic from a medical point of view which directly aims to encounter PD.
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            Melanosomes--dark organelles enlighten endosomal membrane transport.

            Melanosomes are tissue-specific lysosome-related organelles of pigment cells in which melanins are synthesized and stored. Analyses of the trafficking and fate of melanosomal components are beginning to reveal how melanosomes are formed through novel pathways from early endosomal intermediates. These studies unveil generalized structural and functional modifications of the endosomal system in specialized cells, and provide unexpected insights into the biogenesis of multivesicular bodies and how compartmentalization regulates protein refolding. Moreover, genetic disorders that affect the biogenesis of melanosomes and other lysosome-related organelles have shed light onto the molecular machinery that controls specialized endosomal sorting events.
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              Tyramine and octopamine: ruling behavior and metabolism.

              Octopamine (OA) and tyramine (TA) are the invertebrate counterparts of the vertebrate adrenergic transmitters. They are decarboxylation products of the amino acid tyrosine, with TA as the biological precursor of OA. Nevertheless, both compounds are independent neurotransmitters that act through G protein-coupled receptors. OA modulates a plethora of behaviors and peripheral and sense organs, enabling the insect to respond correctly to external stimuli. Because these two phenolamines are the only biogenic amines whose physiological significance is presumably restricted to invertebrates, pharmacologists have focused their attention on the corresponding receptors, which are still believed to represent promising targets for new insecticides. Recent progress made on all levels of OA and TA research has enabled researchers to understand better the molecular events underlying the control of complex behaviors.
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                Author and article information

                Journal
                Exp Anim
                Exp. Anim
                EXPANIM
                Experimental Animals
                Japanese Association for Laboratory Animal Science
                1341-1357
                1881-7122
                26 April 2014
                2014
                : 63
                : 2
                : 107-119
                Affiliations
                [1) ]Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston,TX77030, USA
                [2) ]Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, 1250 Moursund Street, Houston, TX77030, USA
                [3) ]Division of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, 6701 Fannin Street, Houston TX 77030, USA
                Author notes
                Address corresponding: S. Yamamoto, Department of Molecular and Human Genetics, Baylor College of Medicine, 1250 Moursund Street,Houston, TX77030, USA
                Article
                13-0067
                10.1538/expanim.63.107
                4160991
                24770636
                8ba75aa7-9765-43cd-9254-7dded558988a
                ©2014 Japanese Association for Laboratory Animal Science

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License.

                History
                : 20 August 2013
                : 21 October 2013
                Categories
                Review

                behavior,cuticle pigmentation,dopamine,drosophila,genetics
                behavior, cuticle pigmentation, dopamine, drosophila, genetics

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