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

Mihye Lee, Sang Kyoo Paik, Min Jung Lee, Yoon Jung Kim, Sungdae Kim, Minyeop Nahm, Soo Jin Oh, Hyun Man Kim, Jeongbin Yim, C. Justin Lee, Yong Chul Bae, Seungbok Lee

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)250-262
Number of pages13
JournalDevelopmental Biology
Issue number2
Publication statusPublished - 2009 Jun 15

Bibliographical note

Funding Information:
We 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).


  • Atl
  • Drosophila
  • ER and Golgi morphogenesis
  • Hereditary spastic paraplegia
  • Microtubule stability
  • Neuromuscular junction
  • Spastin
  • Synaptic growth

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology


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