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 to form regions of close apposition between the ER and other membranes in the cell, often called membrane contact sites (MCSs).

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2012
Total Cost
$476,393
Indirect Cost
City
State
Country
Zip Code
Murley, Andrew; Sarsam, Reta D; Toulmay, Alexandre et al. (2015) Ltc1 is an ER-localized sterol transporter and a component of ER-mitochondria and ER-vacuole contacts. J Cell Biol 209:539-48
Lahiri, Sujoy; Chao, Jesse T; Tavassoli, Shabnam et al. (2014) A conserved endoplasmic reticulum membrane protein complex (EMC) facilitates phospholipid transfer from the ER to mitochondria. PLoS Biol 12:e1001969
Prinz, William A (2014) Bridging the gap: membrane contact sites in signaling, metabolism, and organelle dynamics. J Cell Biol 205:759-69
Witkin, Keren L; Chong, Yolanda; Shao, Sichen et al. (2012) The budding yeast nuclear envelope adjacent to the nucleolus serves as a membrane sink during mitotic delay. Curr Biol 22:1128-33
Voss, Christiane; Lahiri, Sujoy; Young, Barry P et al. (2012) ER-shaping proteins facilitate lipid exchange between the ER and mitochondria in S. cerevisiae. J Cell Sci 125:4791-9
Toulmay, Alexandre; Prinz, William A (2012) A conserved membrane-binding domain targets proteins to organelle contact sites. J Cell Sci 125:49-58
Liu, Tina Y; Bian, Xin; Sun, Sha et al. (2012) Lipid interaction of the C terminus and association of the transmembrane segments facilitate atlastin-mediated homotypic endoplasmic reticulum fusion. Proc Natl Acad Sci U S A 109:E2146-54
Anwar, Kamran; Klemm, Robin W; Condon, Amanda et al. (2012) The dynamin-like GTPase Sey1p mediates homotypic ER fusion in S. cerevisiae. J Cell Biol 197:209-17
Du, Ximing; Kumar, Jaspal; Ferguson, Charles et al. (2011) A role for oxysterol-binding protein-related protein 5 in endosomal cholesterol trafficking. J Cell Biol 192:121-35
Toulmay, Alexandre; Prinz, William A (2011) Lipid transfer and signaling at organelle contact sites: the tip of the iceberg. Curr Opin Cell Biol 23:458-63

Showing the most recent 10 out of 15 publications