The architecture of the endoplasmic reticulum (ER) consists of an intricate network of sheets and tubules, but how these domains are generated remains largely unknown. The reticulons and reticulon-like proteins are needed to shape the ER. Surprisingly, yeast missing all these proteins are viable and have few phenotypes. To better understand the role of ER-shaping proteins we screened for mutations that cause cells that lack the reticulons to grow poorly. We found that cells lacking the reticulons grow poorly if they are also missing a complex of proteins that tethers the ER and mitochondria. Close contacts between the ER and mitochondria are necessary for efficient lipid exchange between these organelles and mitochondrial biogenesis. We found the phospholipid exchange between the ER and mitochondria slows in cells missing the reticulons and the ER-mitochondria tethering complex. These findings suggest that reticulons are necessary to maintain functional ER-mitochondria contacts. This work is being prepared for submission. In a second project we are working on the role a dynamin-like GTPase called Sey1 in ER-ER fusion and ER biogenesis. We have found that ER-ER fusion slows dramatically in cells missing Sey1 and that Sey1 can mediate fusion of liposomes. Surprisingly, homotypic ER fusion still occurs in cells missing Sey1, suggesting that there is a second fusion pathway. We have evidence that this pathway requires ER SNARE proteins. This work has been submitted for publication. The third project is to identify proteins required for lipid droplet formation in the ER. We have begun to visualize the early steps of lipid droplet biogenesis in the ER. In a fourth project, we have identified novel reticulon-like proteins that help shape the ER in yeast and in higher eukaryotes.

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Hu, Junjie; Shibata, Yoko; Voss, Christiane et al. (2008) Membrane proteins of the endoplasmic reticulum induce high-curvature tubules. Science 319:1247-50
Shibata, Yoko; Voss, Christiane; Rist, Julia M et al. (2008) The reticulon and DP1/Yop1p proteins form immobile oligomers in the tubular endoplasmic reticulum. J Biol Chem 283:18892-904
Federovitch, Christine M; Jones, Ying Z; Tong, Amy H et al. (2008) Genetic and structural analysis of Hmg2p-induced endoplasmic reticulum remodeling in Saccharomyces cerevisiae. Mol Biol Cell 19:4506-20