title: A class of dynamin-like GTPases involved in the generation of the tubular ER network.
abstract: 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.
authors: Howard Hughes Medical Institute, Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
authors: Junjie
authors: J
authors: Hu
authors: Yoko
authors: Y
authors: Shibata
authors: Peng-Peng
authors: PP
authors: Zhu
authors: Christiane
authors: C
authors: Voss
authors: Neggy
authors: N
authors: Rismanchi
authors: William A
authors: WA
authors: Prinz
authors: Tom A
authors: TA
authors: Rapoport
authors: Craig
authors: C
authors: Blackstone
mesh_terms: D000818:Animals; D034284:Dynamin I / Q000378:metabolism*; D034281:Dynamins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: C472231:SEY1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; D034284:Dynamin I; D020558:GTP Phosphohydrolases; D034281:Dynamins