Mutants of the Yeast <i>Yarrowia lipolytica</i>Defective in Protein Exit from the Endoplasmic Reticulum Are Also Defective in Peroxisome Biogenesis

Titorenko, Vladimir I.; Rachubinski, Richard A.

doi:10.1128/mcb.18.5.2789

Cited by 158 publications

(134 citation statements)

References 53 publications

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“…For example, Saccharomyces cerevisiae Pex15p, a tail-anchored type II (N cytosol -C matrix ) PMP, and Yarrowia lipolytica Pex2p and Pex16p are glycosylated within the ER lumen while en route to peroxisomes (15,16). Overexpression of human Pex3p or a portion of the Hansenula polymorpha counterpart fused to a reporter protein resulted in a profound proliferation of ER membranes, consistent with the premise that these proteins are sorted initially to the ER and then to peroxisomes (17,18).…”

supporting

confidence: 61%

The Sorting Signals for Peroxisomal Membrane-bound Ascorbate Peroxidase Are within Its C-terminal Tail

Mullen

Trelease

2000

Journal of Biological Chemistry

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Peroxisomal ascorbate peroxidase (APX) is a carboxyl tail-anchored, type II (N cytosol -C matrix ) integral membrane protein that functions in the regeneration of NAD ؉ in glyoxysomes of germinated oilseeds and protection of peroxisomes in other organisms from toxic H 2 O 2 . Recently we showed that cottonseed peroxisomal APX was sorted post-translationally from the cytosol to peroxisomes via a novel reticular/circular membranous network that was interpreted to be a subdomain of the endoplasmic reticulum (ER), named peroxisomal ER (pER). Here we report on the molecular signals responsible for sorting peroxisomal APX. Deletions or site-specific substitutions of certain amino acid residues within the hydrophilic C-terminal-most eight-amino acid residues (includes a positively charged domain found in most peroxisomal integral membrane-destined proteins) abolished sorting of peroxisomal APX to peroxisomes via pER. However, the C-terminal tail was not sufficient for sorting chloramphenicol acetyltransferase to peroxisomes via pER, whereas the peptide plus most of the immediately adjacent 21-amino acid transmembrane domain (TMD) of peroxisomal APX was sufficient for sorting. Replacement of the peroxisomal APX TMD with an artificial TMD (devoid of putative sorting sequences) plus the peroxisomal APX C-terminal tail also sorted chloramphenicol acetyltransferase to peroxisomes via pER, indicating that the peroxisomal APX TMD does not possess essential sorting information. Instead, the TMD appears to confer the proper context required for the conserved positively charged domain to function within peroxisomal APX as an overlapping pER sorting signal and a membrane peroxisome targeting signal type 2.Peroxisomes are single membrane-bound organelles that do not contain DNA nor protein-synthesizing machinery. Data published thus far indicate that they acquire their nuclearencoded matrix and boundary membrane protein constituents from the cytosol in a regulated, post-translational manner. For instance, proteins destined for the peroxisomal matrix are sorted by at least two evolutionarily conserved targeting signals, the type 1 and type 2 peroxisomal targeting signal (PTS).

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supporting

confidence: 61%

The Sorting Signals for Peroxisomal Membrane-bound Ascorbate Peroxidase Are within Its C-terminal Tail

Mullen

Trelease

2000

Journal of Biological Chemistry

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“…A specific role for the endoplasmic reticulum (ER) in peroxisome biogenesis has been proposed, which may provide an alternative route for synthesis of some peroxisomal proteins (Kunau and Erdmann, 1998;Titorenko and Rachubinski, 1998a;Titorenko and Rachubinski, 2001;Hoepfner et al, 2005). For example, in Yarrowa lipolytica, two pulse-labeled PMPs (Pex2p and Pex16p), were targeted from the cytosol to the ER, and N-glycosylated in the ER and then chased to peroxisomes (Titorenko and Rachubinski, 1998b). In Hansenula polymorha, Pex3p, Pex8p and Pex14p accumulated in the ER in the presence of Brefeldin A (BFA), and can be chased to peroxisomes after removal of BFA (Salomons et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the role of the Endoplasmic Reticulum-Golgi transit in the biogenesis of peroxisomal membrane proteins in wild type and peroxisome biogenesis mutant CHO cells

Toro¹,

Arredondo²,

Córdova³

et al. 2007

Biol. Res.

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Peroxisomes are thought to be formed by division of pre-existing peroxisomes after the import of newly synthesized proteins. However, it has been recently suggested that the endoplasmic reticulum (ER) provides an alternative de novo mechanism for peroxisome biogenesis in some cells. To test a possible role of the ERGolgi transit in peroxisome biogenesis in mammalian cells, we evaluated the biogenesis of three peroxisomal membrane proteins (PMPs): ALDRP (adrenoleukodystrophy related protein), PMP70 and Pex3p in CHO cells. We constructed chimeric genes encoding these PMPs and green fluorescent protein (GFP), and transiently transfected them to wild type and mutant CHO cells, in which normal peroxisomes were replaced by peroxisomal membrane ghosts. The expressed proteins were targeted to peroxisomes and peroxisomal ghosts correctly in the presence or absence of Brefeldin A (BFA), a drug known to block the ER-Golgi transit. Furthermore, low temperature did not disturb the targeting of Pex3p-GFP to peroxisomes. We also constructed two chimeric proteins of PMPs containing an ER retention signal "DEKKMP": GFP-ALDRP-DEKKMP and myc-Pex3p-DEKKMP. These proteins were mostly targeted to peroxisomes. No colocalization with an ER maker was found. These results suggest that the classical ER-Golgi pathway does not play a major role in the biogenesis of mammalian PMPs.

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“…Although a limited number of PMPs first target the endoplasmic reticulum and then traffic to peroxisomes (7)(8)(9)(10)(11), most PMPs are inserted into the peroxisomal membrane directly from the cytosol (12)(13)(14)(15)(16). The direct insertion of PMPs into the peroxisomal membrane is facilitated by Pex19p, a peroxin that is localized predominantly to the cytosol and to a much lesser extent at the surface of peroxisomes (17)(18)(19).…”

mentioning

confidence: 99%

Pex19p Binds Pex30p and Pex32p at Regions Required for Their Peroxisomal Localization but Separate from Their Peroxisomal Targeting Signals

Vizeacoumar

Vreden

Aitchison

et al. 2006

Journal of Biological Chemistry

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The assembly of proteins in the peroxisomal membrane is a multistep process requiring their recognition in the cytosol, targeting to and insertion into the peroxisomal membrane, and stabilization within the lipid bilayer. The peroxin Pex19p has been proposed to be either the receptor that recognizes and targets newly synthesized peroxisomal membrane proteins (PMP) to the peroxisome or a chaperone required for stabilization of PMPs at the peroxisomal membrane. Differentiating between these two roles for The synthesis of nuclear-encoded proteins begins in the cytosol. A protein that is destined for an organelle is directed from the cytosol to the organelle by a sequence or sequences within the protein that contain information essential for targeting the protein to the organelle. These sequences are recognized by receptors in the cytosol or at the target membrane. Having arrived at its specific organelle, the protein is then either translocated across the organelle membrane or inserted into the membrane lipid bilayer.Peroxisomes are ubiquitous organelles that perform a variety of essential biochemical functions, notably in fatty acid metabolism. Mature peroxisomes usually appear as spherical structures in electron micrographs, with diameters of 0.5-1.0 m, and surrounded by a single membrane.

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Mutants of the Yeast Yarrowia lipolyticaDefective in Protein Exit from the Endoplasmic Reticulum Are Also Defective in Peroxisome Biogenesis

Cited by 158 publications

References 53 publications

The Sorting Signals for Peroxisomal Membrane-bound Ascorbate Peroxidase Are within Its C-terminal Tail

The Sorting Signals for Peroxisomal Membrane-bound Ascorbate Peroxidase Are within Its C-terminal Tail

Evaluation of the role of the Endoplasmic Reticulum-Golgi transit in the biogenesis of peroxisomal membrane proteins in wild type and peroxisome biogenesis mutant CHO cells

Pex19p Binds Pex30p and Pex32p at Regions Required for Their Peroxisomal Localization but Separate from Their Peroxisomal Targeting Signals

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