Dataset Information

Nonvesicular phospholipid transfer between peroxisomes and the endoplasmic reticulum.

ABSTRACT: The endoplasmic reticulum (ER) plays an important role in peroxisome biogenesis; some peroxisomal membrane proteins are inserted into the ER and trafficked to peroxisomes in vesicles. These vesicles could also provide the phospholipids required for the growth of peroxisomal membranes, because peroxisomes lack phospholipid biosynthesis enzymes. To test this, we established a novel assay to monitor phospholipid transfer between the ER and peroxisomes and found that phospholipids are rapidly trafficked between these compartments. This transport is not blocked in mutants with conditional defects in Sec proteins required for vesicular trafficking from the ER or in Pex3p, a protein required for peroxisome membrane biogenesis. ER to peroxisome lipid transport was reconstituted in vitro and does not require cytosolic factors or ATP. Our findings indicate that lipids are directly transferred from the ER to peroxisomes by a nonvesicular pathway and suggest that ER to peroxisome vesicular transport is not required to provide lipids for peroxisomal growth.

SUBMITTER: Raychaudhuri S

PROVIDER: S-EPMC2572964 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Publications

Nonvesicular phospholipid transfer between peroxisomes and the endoplasmic reticulum.

Raychaudhuri Sumana S Prinz William A WA

Proceedings of the National Academy of Sciences of the United States of America 20081003 41

The endoplasmic reticulum (ER) plays an important role in peroxisome biogenesis; some peroxisomal membrane proteins are inserted into the ER and trafficked to peroxisomes in vesicles. These vesicles could also provide the phospholipids required for the growth of peroxisomal membranes, because peroxisomes lack phospholipid biosynthesis enzymes. To test this, we established a novel assay to monitor phospholipid transfer between the ER and peroxisomes and found that phospholipids are rapidly traffi ...[more]

PMID: 18836080

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Project description:Tether proteins attach the endoplasmic reticulum (ER) to other cellular membranes, thereby creating contact sites that are proposed to form platforms for regulating lipid homeostasis and facilitating non-vesicular lipid exchange. Sterols are synthesized in the ER and transported by non-vesicular mechanisms to the plasma membrane (PM), where they represent almost half of all PM lipids and contribute critically to the barrier function of the PM. To determine whether contact sites are important for both sterol exchange between the ER and PM and intermembrane regulation of lipid metabolism, we generated Δ-super-tether (Δ-s-tether) yeast cells that lack six previously identified tethering proteins (yeast extended synatotagmin [E-Syt], vesicle-associated membrane protein [VAMP]-associated protein [VAP], and TMEM16-anoctamin homologues) as well as the presumptive tether Ice2. Despite the lack of ER-PM contacts in these cells, ER-PM sterol exchange is robust, indicating that the sterol transport machinery is either absent from or not uniquely located at contact sites. Unexpectedly, we found that the transport of exogenously supplied sterol to the ER occurs more slowly in Δ-s-tether cells than in wild-type (WT) cells. We pinpointed this defect to changes in sterol organization and transbilayer movement within the PM bilayer caused by phospholipid dysregulation, evinced by changes in the abundance and organization of PM lipids. Indeed, deletion of either OSH4, which encodes a sterol/phosphatidylinositol-4-phosphate (PI4P) exchange protein, or SAC1, which encodes a PI4P phosphatase, caused synthetic lethality in Δ-s-tether cells due to disruptions in redundant PI4P and phospholipid regulatory pathways. The growth defect of Δ-s-tether cells was rescued with an artificial "ER-PM staple," a tether assembled from unrelated non-yeast protein domains, indicating that endogenous tether proteins have nonspecific bridging functions. Finally, we discovered that sterols play a role in regulating ER-PM contact site formation. In sterol-depleted cells, levels of the yeast E-Syt tether Tcb3 were induced and ER-PM contact increased dramatically. These results support a model in which ER-PM contact sites provide a nexus for coordinating the complex interrelationship between sterols, sphingolipids, and phospholipids that maintain PM composition and integrity.

Dataset Information

Nonvesicular phospholipid transfer between peroxisomes and the endoplasmic reticulum.

Publications

Nonvesicular phospholipid transfer between peroxisomes and the endoplasmic reticulum.

Similar Datasets

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