Hodge, Christine A. Choudhary, Vineet Wolyniak, Michael J. Scarcelli, John J. Schneiter, Roger Cole, Charles N. 2009-12-16 Cells of <i>Saccharomyces cerevisiae</i> lacking Apq12, a nuclear envelope (NE)-endoplasmic reticulum (ER) integral membrane protein, are defective in assembly of nuclear pore complexes (NPCs), possibly because of defects in regulating membrane fluidity. We identified <i>BRR6</i>, which encodes an essential integral membrane protein of the NE-ER, as a dosage suppressor of <i>apq12</i>δ. Cells carrying the temperature-sensitive <i>brr6-1</i> allele have been shown to have defects in nucleoporin localization, mRNA metabolism and nuclear transport. Electron microscopy revealed that <i>brr6-1</i> cells have gross NE abnormalities and proliferation of the ER. <i>brr6-1</i> cells were hypersensitive to compounds that affect membrane biophysical properties and to inhibitors of lipid biosynthetic pathways, and displayed strong genetic interactions with genes encoding non-essential lipid biosynthetic enzymes. Strikingly, <i>brr6-1</i> cells accumulated, in or near the NE, elevated levels of the two classes of neutral lipids, steryl esters and triacylglycerols, and over-accumulated sterols when they were provided exogenously. Although neutral lipid synthesis is dispensable in wild-type cells, viability of <i>brr6-1</i> cells was fully dependent on neutral lipid production. These data indicate that Brr6 has an essential function in regulating lipid homeostasis in the NE-ER, thereby impacting NPC formation and nucleocytoplasmic transport. application/pdf https://folia.unifr.ch/global/documents/301243 https://folia.unifr.ch/documents/301243/files/schneider_imp.pdf https://folia.unifr.ch/documents/301243/files/schneider_imp_sm.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1242/jcs.055046 info:eu-repo/semantics/openAccess License undefined Journal of Cell Science. - 2010, vol. 123, p. 141-151 Membrane dynamics Nucleocytoplasmic transport Lipid metabolism Nucleoporins Nuclear envelope info:eu-repo/classification/udc/57 Integral membrane proteins Brr6 and Apq12 link assembly of the nuclear pore complex to lipid homeostasis in the endoplasmic reticulum http://purl.org/coar/resource_type/c_6501