Novel Genes Involved in Endosomal Traffic in Yeast Revealed by Suppression of a Targeting-defective Plasma Membrane ATPase Mutant

Luo, Wen; Chang, Amy

doi:10.1083/jcb.138.4.731

Cited by 98 publications

(119 citation statements)

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“…1 A; although vps27 is a suppressor of pma1-7; see ref. 26). These data are consistent with delivery of Pma1-10 from the surface to the vacuole via the prevacuolar compartment.…”

Section: Newly Synthesized Pma1-10 Is Delivered For Vacuolar Degradationsupporting

confidence: 80%

A mutant plasma membrane ATPase, Pma1-10, is defective in stability at the yeast cell surface

Gong

Chang

2001

Proc. Natl. Acad. Sci. U.S.A.

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Pma1 is a plasma membrane H ؉ -ATPase whose activity at the cell surface is essential for cell viability. In this paper we describe a temperature-sensitive pma1 allele, pma1-10 (with two point mutations in the first cytoplasmic loop of Pma1), in which the newly synthesized mutant protein fails to remain stable at the cell surface at 37°C. Instead, Pma1-10 appears to undergo internalization for vacuolar degradation in a manner dependent on End4, Vps27, Doa4, and Pep4. By contrast with wild-type Pma1, mutant Pma1-10 is hypophosphorylated and fails to associate with a Triton-insoluble fraction at 37°C, suggesting failure to enter lipid rafts. Kinetic analysis reveals that, at the permissive temperature, newly synthesized Pma1-10 acquires Triton-insolubility before becoming stabilized. We suggest that phosphorylation and lipid raft association may play important roles in maintaining protein stability at the plasma membrane.

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“…1 A; although vps27 is a suppressor of pma1-7; see ref. 26). These data are consistent with delivery of Pma1-10 from the surface to the vacuole via the prevacuolar compartment.…”

Section: Newly Synthesized Pma1-10 Is Delivered For Vacuolar Degradationsupporting

confidence: 80%

A mutant plasma membrane ATPase, Pma1-10, is defective in stability at the yeast cell surface

Gong

Chang

2001

Proc. Natl. Acad. Sci. U.S.A.

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“…Bsd2p does not appear to be a general receptor for the transport of polypeptides to the vacuole because bsd2 mutations do not impact on the delivery of carboxypeptidase Y (CPY) to the vacuole (37). However, Chang and co-workers have noted that a mutant allele of the plasma membrane proton ATPase, Pma1p (Pma1-7p), is targeted to the vacuole in a Bsd2-dependent manner (37). Presum- ably mutant Pma1-7p adopts a specific conformation that is recognized by the Bsd2p-dependent machinery for vacuole targeting.…”

Section: Discussionmentioning

confidence: 99%

Post-translation Control of Nramp Metal Transport in Yeast

Liu¹,

Culotta

1999

Journal of Biological Chemistry

141

188

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The Saccharomyces cerevisiae SMF1 gene encodes a member of the well conserved family of Nramp metal transport proteins. Previously, we determined that heavy metal uptake by Smf1p was down-regulated by the product of the S. cerevisiae BSD2 gene. We now demonstrate that this regulation occurs at the level of protein stability. In wild type strains, the bulk of Smf1p is normally directed to the vacuole and is rapidly degraded by vacuolar proteases in a PEP4-dependent manner. In bsd2⌬ mutants, Smf1p fails to enter the vacuole, and the Nramp protein is stabilized. Metal ions themselves play an important role in the post-translational regulation of Smf1p. The depletion of heavy metals from the growth medium effects stabilization of Smf1p and additionally results in accumulation of this transporter at the cell surface. Supplementation of manganese alone is sufficient to trigger rapid degradation of Smf1p in a Bsd2p-dependent manner. Together the action of Bsd2p and metal ions provide a rapid and effective means for controlling Nramp metal transport in response to environmental changes.The Nramp family of polypeptides (for natural resistance associated macrophage protein) consists of a group of highly conserved integral membrane proteins thought to play an important role in heavy metal transport. Homologues to Nramp have been identified in animals, plants, and fungi, as well as in certain bacteria (1, 2). Among the most studied are the Nramp1 and Nramp2 genes of rodents. Nramp1 is believed to control the phagosomal accumulation of redox active iron or manganese ions, thereby contributing to an oxygen radical defense against parasitic infection (3-7). Nramp2 is expressed in all tissues and is needed for proper iron absorption and utilization (7-9). In rats, the Nramp2 isoform (DCT1) is induced following iron starvation and exhibits a broad substrate range including essential metals such as zinc, iron, manganese, and copper, as well as the nonessential metals cadmium and lead (10). Transporters such as DCT1/Nramp that act on both essential and toxic metals are expected to fall under tight cellular control.The bakers' yeast Saccharomyces cerevisiae provides an excellent model system in which to study the function and regulation of eukaryotic metal transporters. The high affinity uptake of copper, iron, and zinc in yeast is accomplished by the action of the CTR1, FTR1, and ZTR1 gene products, respectively (11-13). Each of these transport systems is induced under metal-starvation conditions and correspondingly repressed at physiological metal concentrations, and this regulation occurs at the level of CTR1, FTR1, or ZTR1 gene transcription (13)(14)(15)(16)(17)(18)(19) We have previously shown that metal transport by Smf1p is suppressed in yeast by a process involving the product of the BSD2 gene (22). When BSD2 is inactivated by mutation, the transport of copper and cadmium by Smf1p greatly increases, and cells accumulate toxic levels of the metals (22). Bsd2p exhibits an endoplasmic reticulum (ER) 1 localization (22), yet th...

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“…At the Golgi apparatus, sorting of Pma1-7 is controlled by a ubiquitin-dependent quality control system composed of an ubiquitin ligase complex containing Rsp5 and Bul1,2 [15]. From the Golgi, rerouting of the mutant Pma1-7 to the cell surface is restored upon inactivation of the biosynthetic pathway to the vacuole or by sorting defects within the endosomal system [16,17]. Interestingly, surface delivery of Pma1-7 can also be restored by overexpression of Ast1 a peripheral membrane protein that directly interacts with Pma1 and induces clustering of Pma1-7 into SDS/Triton X-100 resistant oligomers [13,18].…”

Section: Biogenesis and Transport Of The Proton Pumping H D -Atpasementioning

confidence: 99%

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

Toulmay

Schneiter

2007

Biochimie

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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.

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Novel Genes Involved in Endosomal Traffic in Yeast Revealed by Suppression of a Targeting-defective Plasma Membrane ATPase Mutant

Cited by 98 publications

References 76 publications

A mutant plasma membrane ATPase, Pma1-10, is defective in stability at the yeast cell surface

A mutant plasma membrane ATPase, Pma1-10, is defective in stability at the yeast cell surface

Post-translation Control of Nramp Metal Transport in Yeast

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

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