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

Cited 39 time in Web of Science Cited 41 time in Scopus
Authors
Lee, Mihye; Paik, Sang Kyoo; Lee, Min-Jung; Kim, Yoon-Jung; Kim, Sungdae; Nahm, Minyeop; Oh, Soo-Jin; Kim, Hyun-Man; Yim, Jeongbin; Lee, C. Justin; Bae, Yong Chul; Lee, Seungbok
Issue Date
2009
Publisher
Elsevier
Citation
Developmental Biology 330 (2009) 250–262
Keywords
AtlSpastinSynaptic growthNeuromuscular junctionER and Golgi morphogenesisMicrotubule stabilityHereditary spastic paraplegiaDrosophila
Abstract
Hereditary 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.
ISSN
0012-1606
Language
English
URI
http://hdl.handle.net/10371/62160
DOI
https://doi.org/10.1016/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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