Lipid-dependent surface transport of the proton pumping ATPase: A model to study plasma membrane biogenesis in yeast

Abstract

The proton pumping H þ -ATPase, Pma1, is one of the most abundant integral membrane proteins of the yeast plasma membrane. Pma1 activity controls the intracellular pH and maintains the electrochemical gradient across the plasma membrane, two essential cellular functions. The maintenance of the proton gradient, on the other hand, also requires a specialized lipid composition of this membrane. The plasma membrane of eukaryotic cells is typically rich in sphingolipids and sterols. These two lipids condense to form less fluid membrane microdomains or lipid rafts. The yeast sphingolipid is peculiar in that it invariably contains a saturated very long-chain fatty acid with 26 carbon atoms. During cell growth and plasma membrane expansion, both C26-containing sphingolipids and Pma1 are first synthesized in the endoplasmatic reticulum from where they are transported by the secretory pathway to the cell surface. Remarkably, shortening the C26 fatty acid to a C22 fatty acid by mutations in the fatty acid elongation complex impairs raft association of newly synthesized Pma1 and induces rapid degradation of the ATPase by rerouting the enzyme from the plasma membrane to the vacuole, the fungal equivalent of the lysosome. Here, we review the role of lipids in mediating raft association and stable surface transport of the newly synthesized ATPase, and discuss a model, in which the newly synthesized ATPase assembles into a membrane environment that is enriched in C26-containing lipids already in the endoplasmatic reticulum. The resulting proteinelipid complex is then transported and sorted as an entity to the plasma membrane. Failure to successfully assemble this lipideprotein complex results in mistargeting of the protein to the vacuole.

Transcriptional Response of Candida parapsilosis following Exposure to Farnesol

“…Changes in the membrane permeability of C. dubliniensis in response to farnesol treatment have also been reported (20). Lipid rafts are associated with specific proteins, such as Pma1p in S. cerevisiae (49) and GPI-anchored proteins in S. cerevisiae (1) and mammalian cells (5). Interestingly, we have shown that several genes involved in GPI anchor biosynthesis have decreased expression in C. parapsilosis following exposure to farnesol, correlating with the changes in the localization of the lipid raft.…”

Orm1 and Orm2 are conserved endoplasmic reticulum membrane proteins regulating lipid homeostasis and protein quality control

“…1C). Because many membrane proteins require a proper lipid environment to achieve their proper conformation (39,40), it seems probable that disrupted lipid balance can increase protein misfolding.…”

Thematic Review Series: Sphingolipids. New insights into sphingolipid metabolism and function in budding yeast

“…Recent studies on the protonpumping H 1 -ATPase, Pma1, reveal some of these functions (90). Pma1 has been a valuable model for determining how proteins are transported from the ER to the plasma membrane, and readers are directed to published reviews for more detailed information (91,92). Like all integral membrane proteins, Pma1 becomes part of the hydrophobic membrane in the ER, where lipids must contribute to the microenvironment necessary for the correct folding of Pma1 into a functional conformation.…”