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 Chu Lee, Seungbok 2024-01-20T21:05:24Z 2024-01-20T21:05:24Z 2021-09-03 2009-06-15 0012-1606 https://pubs.kist.re.kr/handle/201004/132391 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 Ad is required for normal growth of muscles and synapses at the neuromuscular junction (NMJ). Ad protein is highly expressed in larval body-wall muscles. Loss-of-function mutations in the ad 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 Ad. Loss of Ad 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 Ad 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 Ad controls synapse development and ER and Golgi morphogenesis by regulating microtubule stability. (C) 2009 Elsevier Inc. All rights reserved. English ACADEMIC PRESS INC ELSEVIER SCIENCE HEREDITARY SPASTIC PARAPLEGIA TUMOR-SUPPRESSOR GENE ENDOPLASMIC-RETICULUM INTRACELLULAR-TRANSPORT NEUROMUSCULAR-JUNCTION PROTEIN SPASTIN GOLGI-APPARATUS GROWTH SPG3A AXON Drosophila Atlastin regulates the stability of muscle microtubules and is required for synapse development Article 10.1016/j.ydbio.2009.03.019 1 DEVELOPMENTAL BIOLOGY, v.330, no.2, pp.250 - 262 DEVELOPMENTAL BIOLOGY 330 2 250 262 scie scopus 000266574600004 2-s2.0-67349115341 Developmental Biology Developmental Biology Article HEREDITARY SPASTIC PARAPLEGIA TUMOR-SUPPRESSOR GENE ENDOPLASMIC-RETICULUM INTRACELLULAR-TRANSPORT NEUROMUSCULAR-JUNCTION PROTEIN SPASTIN GOLGI-APPARATUS GROWTH SPG3A AXON Drosophila Atl Spastin Synaptic growth Neuromuscular junction ER and Golgi morphogenesis Microtubule stability Hereditary spastic paraplegia