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PMID:20016074

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Citation

Hodge, CA, Choudhary, V, Wolyniak, MJ, Scarcelli, JJ, Schneiter, R and Cole, CN (2010) Integral membrane proteins Brr6 and Apq12 link assembly of the nuclear pore complex to lipid homeostasis in the endoplasmic reticulum. J. Cell. Sci. 123:141-51

Abstract

Cells of Saccharomyces cerevisiae 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 BRR6, which encodes an essential integral membrane protein of the NE-ER, as a dosage suppressor of apq12 Delta. Cells carrying the temperature-sensitive brr6-1 allele have been shown to have defects in nucleoporin localization, mRNA metabolism and nuclear transport. Electron microscopy revealed that brr6-1 cells have gross NE abnormalities and proliferation of the ER. brr6-1 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, brr6-1 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 brr6-1 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.

Links

PubMed PMC2794714 Online version:10.1242/jcs.055046

Keywords

Active Transport, Cell Nucleus/genetics; Cell Nucleus/metabolism; Endoplasmic Reticulum; Lipid Metabolism/genetics; Membrane Fluidity; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mutant Proteins/genetics; Mutant Proteins/metabolism; Nuclear Envelope/genetics; Nuclear Envelope/metabolism; Nuclear Pore/genetics; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/growth & development; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Sterols/metabolism; Temperature; Triglycerides/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

YEAST:APQ12

involved_in

GO:0006998: nuclear envelope organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:APQ12

involved_in

GO:0055088: lipid homeostasis

ECO:0000315: mutant phenotype evidence used in manual assertion

SGD:S000001472
SGD:S000001503
SGD:S000004815

P

Seeded From UniProt

complete

YEAST:APQ12

involved_in

GO:0055088: lipid homeostasis

ECO:0000316: genetic interaction evidence used in manual assertion

SGD:S000000644,SGD:S000005302
SGD:S000001046
SGD:S000001472
SGD:S000001503
SGD:S000003216
SGD:S000004232
SGD:S000004815

P

Seeded From UniProt

complete

YEAST:BRR6

involved_in

GO:0006998: nuclear envelope organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:BRR6

involved_in

GO:0055088: lipid homeostasis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:BRR6

involved_in

GO:0055088: lipid homeostasis

ECO:0000316: genetic interaction evidence used in manual assertion

SGD:S000000007
SGD:S000000630
SGD:S000000644,SGD:S000005302
SGD:S000001302
SGD:S000001472
SGD:S000001503
SGD:S000003732
SGD:S000004046
SGD:S000004232
SGD:S000004364
SGD:S000004467
SGD:S000004617
SGD:S000004815

P

Seeded From UniProt

complete


See also

References

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