A Class of Dynamin-like GTPases Involved in the Generation of the Tubular ER Network

Junjie Hu, Yoko Shibata, Peng Peng Zhu, Christiane Voss, Neggy Rismanchi, William A. Prinz, Tom A. Rapoport, Craig Blackstone

Research output: Contribution to journalArticlepeer-review

410 Scopus citations


The endoplasmic reticulum (ER) consists of tubules that are shaped by the reticulons and DP1/Yop1p, but how the tubules form an interconnected network is unknown. Here, we show that mammalian atlastins, which are dynamin-like, integral membrane GTPases, interact with the tubule-shaping proteins. The atlastins localize to the tubular ER and are required for proper network formation in vivo and in vitro. Depletion of the atlastins or overexpression of dominant-negative forms inhibits tubule interconnections. The Sey1p GTPase in S. cerevisiae is likely a functional ortholog of the atlastins; it shares the same signature motifs and membrane topology and interacts genetically and physically with the tubule-shaping proteins. Cells simultaneously lacking Sey1p and a tubule-shaping protein have ER morphology defects. These results indicate that formation of the tubular ER network depends on conserved dynamin-like GTPases. Since atlastin-1 mutations cause a common form of hereditary spastic paraplegia, we suggest ER-shaping defects as a neuropathogenic mechanism.

Original languageEnglish (US)
Pages (from-to)549-561
Number of pages13
Issue number3
StatePublished - Aug 7 2009
Externally publishedYes



ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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