title: Drosophila Atlastin regulates the stability of muscle microtubules and is required for synapse development.
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 alpha-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.
authors.affiliation: Department of Cell and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-740, Republic of Korea.
authors.forename: Mihye
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authors.lastname: Lee
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authors.initials: SK
authors.lastname: Paik
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Yoon-Jung
authors.initials: YJ
authors.lastname: Kim
authors.forename: Sungdae
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authors.lastname: Kim
authors.forename: Minyeop
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authors.lastname: Nahm
authors.forename: Soo-Jin
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authors.lastname: Kim
authors.forename: Jeongbin
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authors.lastname: Yim
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authors.initials: CJ
authors.lastname: Lee
authors.forename: Yong Chul
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authors.lastname: Bae
authors.forename: Seungbok
authors.initials: S
authors.lastname: Lee