Homotypic fusion of ER membranes requires the dynamin-like GTPase Atlastin

Orso, Genny, Pendin, Diana, Liu, Song, Tosetto, Jessica, Moss, Tyler J., Faust, Joseph E., Micaroni, Massimo, Egorova, Anastasia, Martinuzzi, Andrea, McNew, James A. and Daga, Andrea (2009) Homotypic fusion of ER membranes requires the dynamin-like GTPase Atlastin. Nature, 460 7258: 978-983. doi:10.1038/nature08280

Author Orso, Genny
Pendin, Diana
Liu, Song
Tosetto, Jessica
Moss, Tyler J.
Faust, Joseph E.
Micaroni, Massimo
Egorova, Anastasia
Martinuzzi, Andrea
McNew, James A.
Daga, Andrea
Title Homotypic fusion of ER membranes requires the dynamin-like GTPase Atlastin
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
Publication date 2009-08-20
Year available 2009
Sub-type Article (original research)
DOI 10.1038/nature08280
Open Access Status Not yet assessed
Volume 460
Issue 7258
Start page 978
End page 983
Total pages 6
Editor Dr. Philip Campbell
Place of publication London, UK
Publisher Nature Publishing Group
Language eng
Subject 0601 Biochemistry and Cell Biology
0304 Medicinal and Biomolecular Chemistry
970106 Expanding Knowledge in the Biological Sciences
Abstract Establishment and maintenance of proper architecture is essential for endoplasmic reticulum (ER) function. Homotypic membrane fusion is required for ER biogenesis and maintenance, and has been shown to depend on GTP hydrolysis. Here we demonstrate that Drosophila Atlastin—the fly homologue of the mammalian GTPase atlastin 1 involved in hereditary spastic paraplegia—localizes on ER membranes and that its loss causes ER fragmentation. Drosophila Atlastin embedded in distinct membranes has the ability to form trans-oligomeric complexes and its overexpression induces enlargement of ER profiles, consistent with excessive fusion of ER membranes. In vitro experiments confirm that Atlastin autonomously drives membrane fusion in a GTP-dependent fashion. In contrast, GTPase-deficient Atlastin is inactive, unable to form trans-oligomeric complexes owing to failure to self-associate, and incapable of promoting fusion in vitro. These results demonstrate that Atlastin mediates membrane tethering and fusion and strongly suggest that it is the GTPase activity that is required for ER homotypic fusion.
Keyword Endoplasmic reticulum (ER)
GTP hydrolysis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

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Created: Thu, 03 Sep 2009, 17:41:38 EST by Mr Andrew Martlew on behalf of Institute for Molecular Bioscience