LRRK2 regulates retrograde synaptic compensation at the Drosophila neuromuscular junction
Identifieur interne : 000306 ( Main/Exploration ); précédent : 000305; suivant : 000307LRRK2 regulates retrograde synaptic compensation at the Drosophila neuromuscular junction
Auteurs : Jay Penney [Canada] ; Kazuya Tsurudome [Canada, États-Unis] ; Edward H. Liao [Canada, États-Unis] ; Grant Kauwe [États-Unis] ; Lindsay Gray [États-Unis] ; Akiko Yanagiya [Canada] ; Mario R. Calderon [Canada] ; Nahum Sonenberg [Canada] ; A. Pejmun Haghighi [Canada, États-Unis]Source :
- Nature Communications [ 2041-1723 ] ; 2016.
Abstract
Parkinson's disease gene leucine-rich repeat kinase 2 (LRRK2) has been implicated in a number of processes including the regulation of mitochondrial function, autophagy and endocytic dynamics; nevertheless, we know little about its potential role in the regulation of synaptic plasticity. Here we demonstrate that postsynaptic knockdown of the fly homologue of LRRK2 thwarts retrograde, homeostatic synaptic compensation at the larval neuromuscular junction. Conversely, postsynaptic overexpression of either the fly or human LRRK2 transgene induces a retrograde enhancement of presynaptic neurotransmitter release by increasing the size of the release ready pool of vesicles. We show that LRRK2 promotes cap-dependent translation and identify Furin 1 as its translational target, which is required for the synaptic function of LRRK2. As the regulation of synaptic homeostasis plays a fundamental role in ensuring normal and stable synaptic function, our findings suggest that aberrant function of LRRK2 may lead to destabilization of neural circuits.
Url:
DOI: 10.1038/ncomms12188
PubMed: 27432119
PubMed Central: 4960312
Affiliations:
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Pejmun Haghighi</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Department of Physiology, McGill University</institution>, 3655 Promenade Sir William Osler, Montreal, Quebec,<country>Canada</country> H3G 1Y6</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Buck Institute for Research on Aging</institution>, 8001 Redwood Boulevard, Novato, California 94945,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Parkinson's disease gene leucine-rich repeat kinase 2 (LRRK2) has been implicated in a number of processes including the regulation of mitochondrial function, autophagy and endocytic dynamics; nevertheless, we know little about its potential role in the regulation of synaptic plasticity. Here we demonstrate that postsynaptic knockdown of the fly homologue of LRRK2 thwarts retrograde, homeostatic synaptic compensation at the larval neuromuscular junction. Conversely, postsynaptic overexpression of either the fly or human LRRK2 transgene induces a retrograde enhancement of presynaptic neurotransmitter release by increasing the size of the release ready pool of vesicles. We show that LRRK2 promotes cap-dependent translation and identify Furin 1 as its translational target, which is required for the synaptic function of LRRK2. As the regulation of synaptic homeostasis plays a fundamental role in ensuring normal and stable synaptic function, our findings suggest that aberrant function of LRRK2 may lead to destabilization of neural circuits.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Davis, G W" uniqKey="Davis G">G. W. Davis</name></author><author><name sortKey="Muller, M" uniqKey="Muller M">M. 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Edery</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marygold, S J" uniqKey="Marygold S">S. J. Marygold</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Greggio, E" uniqKey="Greggio E">E. Greggio</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jia, X X" uniqKey="Jia X">X. X. Jia</name></author><author><name sortKey="Gorczyca, M" uniqKey="Gorczyca M">M. Gorczyca</name></author><author><name sortKey="Budnik, V" uniqKey="Budnik V">V. Budnik</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fiala, J C" uniqKey="Fiala J">J. C. Fiala</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Canada</li><li>États-Unis</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Penney, Jay" sort="Penney, Jay" uniqKey="Penney J" first="Jay" last="Penney">Jay Penney</name></noRegion><name sortKey="Haghighi, A Pejmun" sort="Haghighi, A Pejmun" uniqKey="Haghighi A" first="A. Pejmun" last="Haghighi">A. Pejmun Haghighi</name><name sortKey="Liao, Edward H" sort="Liao, Edward H" uniqKey="Liao E" first="Edward H." last="Liao">Edward H. Liao</name><name sortKey="R Calderon, Mario" sort="R Calderon, Mario" uniqKey="R Calderon M" first="Mario" last="R. Calderon">Mario R. Calderon</name><name sortKey="Sonenberg, Nahum" sort="Sonenberg, Nahum" uniqKey="Sonenberg N" first="Nahum" last="Sonenberg">Nahum Sonenberg</name><name sortKey="Tsurudome, Kazuya" sort="Tsurudome, Kazuya" uniqKey="Tsurudome K" first="Kazuya" last="Tsurudome">Kazuya Tsurudome</name><name sortKey="Yanagiya, Akiko" sort="Yanagiya, Akiko" uniqKey="Yanagiya A" first="Akiko" last="Yanagiya">Akiko Yanagiya</name></country><country name="États-Unis"><noRegion><name sortKey="Tsurudome, Kazuya" sort="Tsurudome, Kazuya" uniqKey="Tsurudome K" first="Kazuya" last="Tsurudome">Kazuya Tsurudome</name></noRegion><name sortKey="Gray, Lindsay" sort="Gray, Lindsay" uniqKey="Gray L" first="Lindsay" last="Gray">Lindsay Gray</name><name sortKey="Haghighi, A Pejmun" sort="Haghighi, A Pejmun" uniqKey="Haghighi A" first="A. Pejmun" last="Haghighi">A. Pejmun Haghighi</name><name sortKey="Kauwe, Grant" sort="Kauwe, Grant" uniqKey="Kauwe G" first="Grant" last="Kauwe">Grant Kauwe</name><name sortKey="Liao, Edward H" sort="Liao, Edward H" uniqKey="Liao E" first="Edward H." last="Liao">Edward H. Liao</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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