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

Title
Drosophila atlastin regulates the stability of muscle microtubules and is required for synapse development
Authors
이미혜백상규이민정김윤정김성대남민엽오수진김현만임정빈이창준배용철이승복
Keywords
Drosophila; Atl; Spastin; Synaptic growth; Neuromuscular junction; ER and Golgi morphogenesis; Microtubule stability; Hereditary spastic paraplegia
Issue Date
2009-06
Publisher
Developmental biology
Citation
VOL 330, NO 2, 250-262
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.
URI
http://pubs.kist.re.kr/handle/201004/35112
ISSN
0012-1606
Appears in Collections:
KIST Publication > Article
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE