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Drosophila Atlastin regulates the stability of muscle microtubules and is required for synapse development

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dc.contributor.authorLee, Mihye-
dc.contributor.authorPaik, Sang Kyoo-
dc.contributor.authorLee, Min-Jung-
dc.contributor.authorKim, Yoon-Jung-
dc.contributor.authorKim, Sungdae-
dc.contributor.authorNahm, Minyeop-
dc.contributor.authorOh, Soo-Jin-
dc.contributor.authorKim, Hyun-Man-
dc.contributor.authorYim, Jeongbin-
dc.contributor.authorLee, C. Justin-
dc.contributor.authorBae, Yong Chul-
dc.contributor.authorLee, Seungbok-
dc.date.accessioned2010-03-31T01:47:47Z-
dc.date.available2010-03-31T01:47:47Z-
dc.date.issued2009-
dc.identifier.citationDevelopmental Biology 330 (2009) 250–262en
dc.identifier.issn0012-1606-
dc.identifier.urihttps://hdl.handle.net/10371/62160-
dc.description.abstractHereditary spastic paraplegia (HSP) is an inherited neurological disorder characterized by progressive spasticity and weakness of the lower extremities. The most common early-onset form of HSP is caused by mutations in the human gene that encodes the dynamin-family GTPase Atlastin-1 (Atl-1). Recently, loss of the Drosophila ortholog of Atl-1 (Atl) has been found to induce locomotor impairments from the earliest adult stages, suggesting the developmental role of atlastin-subfamily GTPases. Here, we provide evidence that Atl is required for normal growth of muscles and synapses at the neuromuscular junction (NMJ). Atl protein is highly expressed in larval body-wall muscles. Loss-of-function mutations in the atl gene reduce the size of muscles and increase the number of synaptic boutons. Rescue of these defects is accomplished by muscular, but not neuronal expression of Atl. Loss of Atl also disrupts ER and Golgi morphogenesis in muscles and reduces the synaptic levels of the scaffold proteins Dlg and α-spectrin. We also provide evidence that Atl functions with the microtubule-severing protein Spastin to disassemble microtubules in muscles. Finally, we demonstrate that the microtubule-destabilizing drug vinblastine alleviates synapse and muscle defects in atl mutants. Together, our results suggest that Atl controls synapse development and ER and Golgi morphogenesis by regulating microtubule stability.en
dc.description.sponsorshipWe thank Dr. Jaesang Kim for comments on the manuscript. We are grateful to Drs. Mary A. Lilly, Young-Ho Koh, Nina T. Sherwood, and Jaeseob Kim for fly stocks. This work was supported by grants from the Research Program for New Drug Target Discovery (M10748000283-07N4800-28310), the Brain Research Center of the 21st Century Frontier (M103KV010002-06K2201-00210), the Basic Research Program of the Korea Science and Engineering Foundation (R01-2006-000-10487-0), and the Korea Research Foundation (KRF-2006-312-C00361).en
dc.language.isoenen
dc.publisherElsevieren
dc.subjectAtlen
dc.subjectSpastinen
dc.subjectSynaptic growthen
dc.subjectNeuromuscular junctionen
dc.subjectER and Golgi morphogenesisen
dc.subjectMicrotubule stabilityen
dc.subjectHereditary spastic paraplegiaen
dc.subjectDrosophilaen
dc.titleDrosophila Atlastin regulates the stability of muscle microtubules and is required for synapse developmenten
dc.typeArticleen
dc.contributor.AlternativeAuthor이미혜-
dc.contributor.AlternativeAuthor백상규-
dc.contributor.AlternativeAuthor이민정-
dc.contributor.AlternativeAuthor김윤정-
dc.contributor.AlternativeAuthor김성대-
dc.contributor.AlternativeAuthor남민엽-
dc.contributor.AlternativeAuthor오수진-
dc.contributor.AlternativeAuthor김현만-
dc.contributor.AlternativeAuthor임정빈-
dc.contributor.AlternativeAuthor배용철-
dc.contributor.AlternativeAuthor이승복-
dc.identifier.doi10.1016/j.ydbio.2009.03.019-
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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