Leucine-rich repeat kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease
Identifieur interne : 001F19 ( Main/Exploration ); précédent : 001F18; suivant : 001F20Leucine-rich repeat kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease
Auteurs : Katerina Venderova ; Ghassan Kabbach ; Elizabeth Abdel-Messih ; Yi Zhang ; Robin J. Parks ; Yuzuru Imai ; Stephan Gehrke ; Johnny Ngsee ; Matthew J. Lavoie ; Ruth S. Slack ; Yong Rao [Canada] ; Zhuohua Zhang [États-Unis] ; Bingwei Lu ; M. Emdadul Haque [Canada] ; David S. Park [Canada]Source :
- Human Molecular Genetics [ 0964-6906 ] ; 2009-11-15.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Génétique.
English descriptors
- KwdEn :
- Animals, Animals, Genetically Modified, Disease Models, Animal, Drosophila melanogaster, Drosophila melanogaster (genetics), Drosophila melanogaster (metabolism), Female, Genetics, Humans, Intracellular Signaling Peptides and Proteins (genetics), Intracellular Signaling Peptides and Proteins (metabolism), Kinase, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Leucine-rich repeat, Life Expectancy, Male, Models, Oncogene Proteins (genetics), Oncogene Proteins (metabolism), Parkinson Disease (genetics), Parkinson Disease (metabolism), Parkinson Disease (physiopathology), Parkinson disease, Protein Binding, Protein Deglycase DJ-1, Protein Kinases (genetics), Protein Kinases (metabolism), Protein-Serine-Threonine Kinases (genetics), Protein-Serine-Threonine Kinases (metabolism), Ubiquitin-Protein Ligases (genetics), Ubiquitin-Protein Ligases (metabolism).
- MESH :
- chemical , genetics : Intracellular Signaling Peptides and Proteins, Oncogene Proteins, Protein Kinases, Protein-Serine-Threonine Kinases, Ubiquitin-Protein Ligases.
- genetics : Drosophila melanogaster, Parkinson Disease.
- metabolism : Drosophila melanogaster, Intracellular Signaling Peptides and Proteins, Oncogene Proteins, Parkinson Disease, Protein Kinases, Protein-Serine-Threonine Kinases, Ubiquitin-Protein Ligases.
- physiopathology : Parkinson Disease.
- Animals, Animals, Genetically Modified, Disease Models, Animal, Female, Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Life Expectancy, Male, Protein Binding, Protein Deglycase DJ-1.
Abstract
Mutations in the LRRK2 gene are the most common genetic cause of familial Parkinson's disease (PD). However, its physiological and pathological functions are unknown. Therefore, we generated several independent Drosophila lines carrying WT or mutant human LRRK2 (mutations in kinase, COR or LRR domains, resp.). Ectopic expression of WT or mutant LRRK2 in dopaminergic neurons caused their significant loss accompanied by complex age-dependent changes in locomotor activity. Overall, the ubiquitous expression of LRRK2 increased lifespan and fertility of the flies. However, these flies were more sensitive to rotenone. LRRK2 expression in the eye exacerbated retinal degeneration. Importantly, in double transgenic flies, various indices of the eye and dopaminergic survival were modified in a complex fashion by a concomitant expression of PINK1, DJ-1 or Parkin. This evidence suggests a genetic interaction between these PD-relevant genes.
Url:
DOI: 10.1093/hmg/ddp394
Affiliations:
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Le document en format XML
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Parks</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Imai, Yuzuru" sort="Imai, Yuzuru" uniqKey="Imai Y" first="Yuzuru" last="Imai">Yuzuru Imai</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Gehrke, Stephan" sort="Gehrke, Stephan" uniqKey="Gehrke S" first="Stephan" last="Gehrke">Stephan Gehrke</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Ngsee, Johnny" sort="Ngsee, Johnny" uniqKey="Ngsee J" first="Johnny" last="Ngsee">Johnny Ngsee</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Lavoie, Matthew J" sort="Lavoie, Matthew J" uniqKey="Lavoie M" first="Matthew J." last="Lavoie">Matthew J. Lavoie</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Slack, Ruth S" sort="Slack, Ruth S" uniqKey="Slack R" first="Ruth S." last="Slack">Ruth S. Slack</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Rao, Yong" sort="Rao, Yong" uniqKey="Rao Y" first="Yong" last="Rao">Yong Rao</name><affiliation wicri:level="1"><country>Canada</country><wicri:regionArea>Center for Research in Neuroscience, University McGill, Montreal, Quebec</wicri:regionArea><wicri:noRegion>Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Zhuohua" sort="Zhang, Zhuohua" uniqKey="Zhang Z" first="Zhuohua" last="Zhang">Zhuohua Zhang</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Burnham Institute for Medical Research, La Jolla, CA 92037</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Lu, Bingwei" sort="Lu, Bingwei" uniqKey="Lu B" first="Bingwei" last="Lu">Bingwei Lu</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Haque, M Emdadul" sort="Haque, M Emdadul" uniqKey="Haque M" first="M. Emdadul" last="Haque">M. Emdadul Haque</name><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Canada</country></affiliation></author><author><name sortKey="Park, David S" sort="Park, David S" uniqKey="Park D" first="David S." last="Park">David S. Park</name><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Canada</country></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Molecular Genetics</title><idno type="ISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2009-11-15">2009-11-15</date><biblScope unit="volume">18</biblScope><biblScope unit="issue">22</biblScope><biblScope unit="page" from="4390">4390</biblScope><biblScope unit="page" to="4404">4404</biblScope></imprint><idno type="ISSN">0964-6906</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0964-6906</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Animals, Genetically Modified</term><term>Disease Models, Animal</term><term>Drosophila melanogaster</term><term>Drosophila melanogaster (genetics)</term><term>Drosophila melanogaster (metabolism)</term><term>Female</term><term>Genetics</term><term>Humans</term><term>Intracellular Signaling Peptides and Proteins (genetics)</term><term>Intracellular Signaling Peptides and Proteins (metabolism)</term><term>Kinase</term><term>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</term><term>Leucine-rich repeat</term><term>Life Expectancy</term><term>Male</term><term>Models</term><term>Oncogene Proteins (genetics)</term><term>Oncogene Proteins (metabolism)</term><term>Parkinson Disease (genetics)</term><term>Parkinson Disease (metabolism)</term><term>Parkinson Disease (physiopathology)</term><term>Parkinson disease</term><term>Protein Binding</term><term>Protein Deglycase DJ-1</term><term>Protein Kinases (genetics)</term><term>Protein Kinases (metabolism)</term><term>Protein-Serine-Threonine Kinases (genetics)</term><term>Protein-Serine-Threonine Kinases (metabolism)</term><term>Ubiquitin-Protein Ligases (genetics)</term><term>Ubiquitin-Protein Ligases (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Intracellular Signaling Peptides and Proteins</term><term>Oncogene Proteins</term><term>Protein Kinases</term><term>Protein-Serine-Threonine Kinases</term><term>Ubiquitin-Protein Ligases</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Drosophila melanogaster</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Drosophila melanogaster</term><term>Intracellular Signaling Peptides and Proteins</term><term>Oncogene Proteins</term><term>Parkinson Disease</term><term>Protein Kinases</term><term>Protein-Serine-Threonine Kinases</term><term>Ubiquitin-Protein Ligases</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><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>Female</term><term>Humans</term><term>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</term><term>Life Expectancy</term><term>Male</term><term>Protein Binding</term><term>Protein Deglycase DJ-1</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Domaine répété riche en leucine</term><term>Drosophila melanogaster</term><term>Génétique</term><term>Kinase</term><term>Maladie de Parkinson</term><term>Modèle</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract">Mutations in the LRRK2 gene are the most common genetic cause of familial Parkinson's disease (PD). However, its physiological and pathological functions are unknown. Therefore, we generated several independent Drosophila lines carrying WT or mutant human LRRK2 (mutations in kinase, COR or LRR domains, resp.). Ectopic expression of WT or mutant LRRK2 in dopaminergic neurons caused their significant loss accompanied by complex age-dependent changes in locomotor activity. Overall, the ubiquitous expression of LRRK2 increased lifespan and fertility of the flies. However, these flies were more sensitive to rotenone. LRRK2 expression in the eye exacerbated retinal degeneration. Importantly, in double transgenic flies, various indices of the eye and dopaminergic survival were modified in a complex fashion by a concomitant expression of PINK1, DJ-1 or Parkin. This evidence suggests a genetic interaction between these PD-relevant genes.</div></front></TEI><affiliations><list><country><li>Canada</li><li>États-Unis</li></country><region><li>Californie</li></region></list><tree><noCountry><name sortKey="Abdel Messih, Elizabeth" sort="Abdel Messih, Elizabeth" uniqKey="Abdel Messih E" first="Elizabeth" last="Abdel-Messih">Elizabeth Abdel-Messih</name><name sortKey="Gehrke, Stephan" sort="Gehrke, Stephan" uniqKey="Gehrke S" first="Stephan" last="Gehrke">Stephan Gehrke</name><name sortKey="Imai, Yuzuru" sort="Imai, Yuzuru" uniqKey="Imai Y" first="Yuzuru" last="Imai">Yuzuru Imai</name><name sortKey="Kabbach, Ghassan" sort="Kabbach, Ghassan" uniqKey="Kabbach G" first="Ghassan" last="Kabbach">Ghassan Kabbach</name><name sortKey="Lavoie, Matthew J" sort="Lavoie, Matthew J" uniqKey="Lavoie M" first="Matthew J." last="Lavoie">Matthew J. Lavoie</name><name sortKey="Lu, Bingwei" sort="Lu, Bingwei" uniqKey="Lu B" first="Bingwei" last="Lu">Bingwei Lu</name><name sortKey="Ngsee, Johnny" sort="Ngsee, Johnny" uniqKey="Ngsee J" first="Johnny" last="Ngsee">Johnny Ngsee</name><name sortKey="Parks, Robin J" sort="Parks, Robin J" uniqKey="Parks R" first="Robin J." last="Parks">Robin J. Parks</name><name sortKey="Slack, Ruth S" sort="Slack, Ruth S" uniqKey="Slack R" first="Ruth S." last="Slack">Ruth S. Slack</name><name sortKey="Venderova, Katerina" sort="Venderova, Katerina" uniqKey="Venderova K" first="Katerina" last="Venderova">Katerina Venderova</name><name sortKey="Zhang, Yi" sort="Zhang, Yi" uniqKey="Zhang Y" first="Yi" last="Zhang">Yi Zhang</name></noCountry><country name="Canada"><noRegion><name sortKey="Rao, Yong" sort="Rao, Yong" uniqKey="Rao Y" first="Yong" last="Rao">Yong Rao</name></noRegion><name sortKey="Haque, M Emdadul" sort="Haque, M Emdadul" uniqKey="Haque M" first="M. Emdadul" last="Haque">M. Emdadul Haque</name><name sortKey="Park, David S" sort="Park, David S" uniqKey="Park D" first="David S." last="Park">David S. Park</name></country><country name="États-Unis"><region name="Californie"><name sortKey="Zhang, Zhuohua" sort="Zhang, Zhuohua" uniqKey="Zhang Z" first="Zhuohua" last="Zhang">Zhuohua Zhang</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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