Inhibition of Atg6 and Pi3K59F autophagy genes in neurons decreases lifespan and locomotor ability in Drosophila melanogaster.
Identifieur interne : 000315 ( Main/Exploration ); précédent : 000314; suivant : 000316Inhibition of Atg6 and Pi3K59F autophagy genes in neurons decreases lifespan and locomotor ability in Drosophila melanogaster.
Auteurs : P G M'Angale [Canada] ; B E Staveley [Canada]Source :
- Genetics and molecular research : GMR [ 1676-5680 ] ; 2016.
English descriptors
- KwdEn :
- Animals, Animals, Genetically Modified, Autophagy (genetics), Beclin-1 (biosynthesis), Beclin-1 (genetics), Disease Models, Animal, Dopa Decarboxylase (biosynthesis), Dopa Decarboxylase (genetics), Drosophila Proteins (biosynthesis), Drosophila Proteins (genetics), Drosophila melanogaster (genetics), Eye (growth & development), Eye (metabolism), Gene Expression Regulation, Developmental, Humans, Longevity (genetics), Motor Activity (genetics), Neurons (metabolism), Neurons (pathology), Parkinson Disease (genetics), Parkinson Disease (pathology), RNA Interference, alpha-Synuclein (genetics).
- MESH :
- chemical , biosynthesis : Beclin-1, Dopa Decarboxylase, Drosophila Proteins.
- genetics : Autophagy, Beclin-1, Dopa Decarboxylase, Drosophila Proteins, Drosophila melanogaster, Longevity, Motor Activity, Parkinson Disease, alpha-Synuclein.
- growth & development : Eye.
- metabolism : Eye, Neurons.
- pathology : Neurons, Parkinson Disease.
- Animals, Animals, Genetically Modified, Disease Models, Animal, Gene Expression Regulation, Developmental, Humans, RNA Interference.
Abstract
Autophagy is a cellular mechanism implicated in the pathology of Parkinson's disease. The proteins Atg6 (Beclin 1) and Pi3K59F are involved in autophagosome formation, a key step in the initiation of autophagy. We first used the GMR-Gal4 driver to determine the effect of reducing the expression of the genes encoding these proteins on the developing Drosophila melanogaster eye. Subsequently, we inhibited their expression in D. melanogaster neurons under the direction of a Dopa decarboxylase (Ddc) transgene, and examined the effects on longevity and motor function. Decreased longevity coupled with an age-dependent loss of climbing ability was observed. In addition, we investigated the roles of these genes in the well-studied α-synuclein-induced Drosophila model of Parkinson's disease. In this context, lowered expression of Atg6 or Pi3K59F in Ddc-Gal4-expressing neurons results in decreased longevity and associated age-dependent loss of locomotor ability. Inhibition of Atg6 or Pi3K59F together with overexpression of the sole pro-survival Bcl-2 Drosophila homolog Buffy in Ddc-Gal4-expressing neurons resulted in further decrease in the survival and climbing ability of Atg6-RNAi flies, whereas these measures were ameliorated in Pi3K59F-RNAi flies.
DOI: 10.4238/gmr15048953
PubMed: 27813607
Affiliations:
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Newfoundland and Labrador, Canada bestave@mun.ca.</nlm:affiliation><country wicri:rule="url">Canada</country><wicri:regionArea>Department of Biology, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador</wicri:regionArea><wicri:noRegion>Newfoundland and Labrador</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27813607</idno><idno type="pmid">27813607</idno><idno type="doi">10.4238/gmr15048953</idno><idno type="wicri:Area/PubMed/Corpus">000135</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000135</idno><idno type="wicri:Area/PubMed/Curation">000135</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000135</idno><idno type="wicri:Area/PubMed/Checkpoint">000135</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000135</idno><idno 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Labrador</wicri:regionArea><wicri:noRegion>Newfoundland and Labrador</wicri:noRegion></affiliation></author><author><name sortKey="Staveley, B E" sort="Staveley, B E" uniqKey="Staveley B" first="B E" last="Staveley">B E Staveley</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biology, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada bestave@mun.ca.</nlm:affiliation><country wicri:rule="url">Canada</country><wicri:regionArea>Department of Biology, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador</wicri:regionArea><wicri:noRegion>Newfoundland and Labrador</wicri:noRegion></affiliation></author></analytic><series><title level="j">Genetics and molecular research : GMR</title><idno type="eISSN">1676-5680</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Animals, Genetically Modified</term><term>Autophagy (genetics)</term><term>Beclin-1 (biosynthesis)</term><term>Beclin-1 (genetics)</term><term>Disease Models, Animal</term><term>Dopa Decarboxylase (biosynthesis)</term><term>Dopa Decarboxylase (genetics)</term><term>Drosophila Proteins (biosynthesis)</term><term>Drosophila Proteins (genetics)</term><term>Drosophila melanogaster (genetics)</term><term>Eye (growth & development)</term><term>Eye (metabolism)</term><term>Gene Expression Regulation, Developmental</term><term>Humans</term><term>Longevity (genetics)</term><term>Motor Activity (genetics)</term><term>Neurons (metabolism)</term><term>Neurons (pathology)</term><term>Parkinson Disease (genetics)</term><term>Parkinson Disease (pathology)</term><term>RNA Interference</term><term>alpha-Synuclein (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Beclin-1</term><term>Dopa Decarboxylase</term><term>Drosophila Proteins</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Autophagy</term><term>Beclin-1</term><term>Dopa Decarboxylase</term><term>Drosophila Proteins</term><term>Drosophila melanogaster</term><term>Longevity</term><term>Motor Activity</term><term>Parkinson Disease</term><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Eye</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Eye</term><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Neurons</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Animals, Genetically Modified</term><term>Disease Models, Animal</term><term>Gene Expression Regulation, Developmental</term><term>Humans</term><term>RNA Interference</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Autophagy is a cellular mechanism implicated in the pathology of Parkinson's disease. The proteins Atg6 (Beclin 1) and Pi3K59F are involved in autophagosome formation, a key step in the initiation of autophagy. We first used the GMR-Gal4 driver to determine the effect of reducing the expression of the genes encoding these proteins on the developing Drosophila melanogaster eye. Subsequently, we inhibited their expression in D. melanogaster neurons under the direction of a Dopa decarboxylase (Ddc) transgene, and examined the effects on longevity and motor function. Decreased longevity coupled with an age-dependent loss of climbing ability was observed. In addition, we investigated the roles of these genes in the well-studied α-synuclein-induced Drosophila model of Parkinson's disease. In this context, lowered expression of Atg6 or Pi3K59F in Ddc-Gal4-expressing neurons results in decreased longevity and associated age-dependent loss of locomotor ability. Inhibition of Atg6 or Pi3K59F together with overexpression of the sole pro-survival Bcl-2 Drosophila homolog Buffy in Ddc-Gal4-expressing neurons resulted in further decrease in the survival and climbing ability of Atg6-RNAi flies, whereas these measures were ameliorated in Pi3K59F-RNAi flies.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="M Angale, P G" sort="M Angale, P G" uniqKey="M Angale P" first="P G" last="M'Angale">P G M'Angale</name></noRegion><name sortKey="Staveley, B E" sort="Staveley, B E" uniqKey="Staveley B" first="B E" last="Staveley">B E Staveley</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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