Atlastin-1, the dynamin-like GTPase responsible for spastic paraplegia SPG3A, remodels lipid membranes and may form tubules and vesicles in the endoplasmic reticulum.

We examined the effects of wild-type and mutant atlastin-1 on vesicletransport in the endoplasmic reticulum (ER)-Golgi interface and vesiclebudding from ER-derived microsomes using the temperature-sensitive reporter vesicular stomatitis virusglycoprotein (VSV-G), and the ability of purified atlastin-1 to form tubulesor vesiclesfrom protein-free phosphatidylserineliposomes. A GTPasedomain mutation (T162P) altered the cellular distribution of the ER, but none of the mutations studied significantly affected transport from the ER to the Golgi apparatus. The mutations also had no significant effect on the incorporation of VSV-G into vesiclesformed from ER microsomes. Atlastin-1, however, was also incorporated into microsome-derived vesicles, suggesting that it might be implicated in vesicleformation. Purified atlastin-1 transformed phosphatidylserineliposomes into branched tubulesand polygonal networks of tubulesand vesicles, an action inhibited by GDP and the synthetic dynamininhibitor dynasore. The GTPasemutations T162P and R217C decreased but did not totally prevent this action; the C-terminal transmembrane domain mutation R495W was as active as the wild-type enzyme. Similar effects were observed in human embryonic kidney cells over-expressing mutant atlastin-1. We concluded that atlastin-1, like dynamin, might be implicated in membrane tubulationand vesiculation and participated in the formation as well as the function of the ER.