Pex3p Initiates the Formation of a Preperoxisomal Compartment from a Subdomain of the Endoplasmic Reticulum in Saccharomyces cerevisiae

Peroxisomes are dynamic organelles that often proliferate in response to compounds that they metabolize. Peroxisomes can proliferate by two apparent mechanisms, division of preexisting peroxisomes and de novo synthesis of peroxisomes. Evidence for de novo peroxisome synthesis comes from studies of cells lacking the peroxisomal integral membrane peroxin Pex3p. These cells lack peroxisomes, but peroxisomes can assemble upon reintroduction of Pex3p. The source of these peroxisomes has been the subject of debate. Here, we show that the amino-terminal 46 amino acids of Pex3p of Saccharomyces cerevisiae target to a subdomain of the endoplasmic reticulum and initiate the formation of a preperoxisomal compartment for de novo peroxisome synthesis. In vivo video microscopy showed that this preperoxisomal compartment can import both peroxisomal matrix and membrane proteins leading to the formation of bona fide peroxisomes through the continued activity of full-length Pex3p. Peroxisome formation from the preperoxisomal compartment depends on the activity of the genes PEX14 and PEX19, which are required for the targeting of peroxisomal matrix and membrane proteins, respectively. Our findings support a direct role for the endoplasmic reticulum in de novo peroxisome formation. Peroxisomes are dynamic organelles that often proliferate in response to compounds that they metabolize. Peroxisomes can proliferate by two apparent mechanisms, division of preexisting peroxisomes and de novo synthesis of peroxisomes. Evidence for de novo peroxisome synthesis comes from studies of cells lacking the peroxisomal integral membrane peroxin Pex3p. These cells lack peroxisomes, but peroxisomes can assemble upon reintroduction of Pex3p. The source of these peroxisomes has been the subject of debate. Here, we show that the amino-terminal 46 amino acids of Pex3p of Saccharomyces cerevisiae target to a subdomain of the endoplasmic reticulum and initiate the formation of a preperoxisomal compartment for de novo peroxisome synthesis. In vivo video microscopy showed that this preperoxisomal compartment can import both peroxisomal matrix and membrane proteins leading to the formation of bona fide peroxisomes through the continued activity of full-length Pex3p. Peroxisome formation from the preperoxisomal compartment depends on the activity of the genes PEX14 and PEX19, which are required for the targeting of peroxisomal matrix and membrane proteins, respectively. Our findings support a direct role for the endoplasmic reticulum in de novo peroxisome formation. A characteristic of eukaryotic cells is the presence of seemingly distinct subcellular compartments or organelles possessing specific sets of proteins required for specialized cellular functions. However, organelles do not exist in isolation, and interorganellar communication through the movement and exchange of different molecules is required for normal cell function. This interdependence of organelles extends beyond their biochemical and metabolic roles and necessitates that their biogenesis and turnover also be coordinated. The peroxisome has long been considered an autonomous organelle that proliferates by the growth and division of preexisting peroxisomes (1Lazarow P.B. Fujiki Y. Annu. Rev. Cell Biol. 1985; 1: 489-530Crossref PubMed Scopus (890) Google Scholar) and is inherited as a functional organelle at cell division. But what of the concept of de novo peroxisome biogenesis? From an evolutionary point of view, peroxisome proliferation and inheritance could have evolved as a response to a slow and perhaps unreliable mechanism of de novo peroxisome biogenesis. However, de novo peroxisome biogenesis, when combined with peroxisome growth, division, and inheritance, would provide the cell with a fail-safe system for peroxisome maintenance and ultimately for its survival. Evidence implicating the endoplasmic reticulum (ER) 3The abbreviations used are: ER, endoplasmic reticulum; mRFP, monomeric red fluorescent protein; PTS, peroxisome targeting signal; GFP, green fluorescent protein; CSM, complete supplement mixture; RIM, raffinose induction medium; GIM, galactose induction medium. in peroxisome biogenesis has accumulated in recent years (reviewed in Refs. 2Tabak H.F. Braakman I. Distel B. Trends Cell Biol. 1999; 9: 447-453Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar, 3Titorenko V.I. Rachubinski R.A. Nat. Rev. Mol. Cell Biol. 2001; 2: 357-368Crossref PubMed Scopus (158) Google Scholar, 4Eckert J.H. Erdmann R. Rev. Physiol. Biochem. Pharmacol. 2003; 147: 75-121Crossref PubMed Scopus (82) Google Scholar). The amino-terminal 16 amino acids of the peroxisomal integral membrane protein Pex3p of Hansenula polymorpha were shown to be sufficient to target a reporter protein to the ER (5Baerends R.J. Rasmussen S.W. Hilbrands R.E. van der Heide M. Faber K.N. Reuvekamp P.T.W. Kiel J.A. Cregg J.M. van der Klei I. Veenhuis M. J. Biol. Chem. 1996; 271: 8887-8894Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar), whereas treatment of cells of this yeast with brefeldin A led to the accumulation of newly synthesized peroxisomal membrane and matrix proteins at the ER (6Salomons F.A. van der Klei I Kram A.M. Harder W. Veenhuis M. FEBS Lett. 1997; 411: 133-139Crossref PubMed Scopus (50) Google Scholar). In the yeast Yarrowia lipolytica, the peroxisomal membrane proteins Pex2p and Pex16p were shown to traffic through the ER and to acquire core N-linked glycosylation (7Titorenko V.I. Ogrydziak D.M. Rachubinski R.A. Mol. Cell. Biol. 1997; 17: 5210-5226Crossref PubMed Scopus (109) Google Scholar). Findings supporting de novo peroxisome biogenesis in close association with the ER were obtained in cells of Y. lipolytica temperature-sensitive for Pex3p function (8Bascom R.A. Chan H. Rachubinski R.A. Mol. Biol. Cell. 2003; 14: 939-957Crossref PubMed Scopus (44) Google Scholar), and studies in the plant Arabidopsis showed that peroxisomal ascorbate peroxidase localized to a subdomain of rough ER that could serve as a compartment for posttranslational sorting to peroxisomes (9Lisenbee C.S. Heinze M. Trelease R.N. Plant Physiol. 2003; 132: 870-882Crossref PubMed Scopus (63) Google Scholar). In mouse dendritic cells, the peroxisomal membrane proteins Pex13p and PMP70 were found in subdomains of the ER that extended to a peroxisomal reticulum from which mature peroxisome arose (10Geuze H.J. Murk J.L. Stroobants A.K. Griffith J.M. Kleijmeer M.J. Koster A.J. Verkleij A.J. Distel B. Tabak H.F. Mol. Biol. Cell. 2003; 14: 2900-2907Crossref PubMed Scopus (148) Google Scholar). Little is known about the very early events of peroxisome biogenesis, particularly the formation of the peroxisome membrane. Only Pex3p, Pex16p, and Pex19p have been shown to have specific roles in biogenesis of the peroxisome membrane. Human cells lacking any of these peroxins contain neither peroxisomes nor peroxisome remnants (11Matsuzono Y. Kinoshita N. Tamura S. Shimozawa N. Hamasaki M. Ghaedi K. Wanders R.J. Suzuki Y. Kondo N. Fujiki Y. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 2116-2121Crossref PubMed Scopus (189) Google Scholar, 12South S.T. Gould S.J. J. Cell Biol. 1999; 144: 255-266Crossref PubMed Scopus (193) Google Scholar, 13Ghaedi K. Tamura S. Okumoto K. Matsuzono Y. Fujiki Y. Mol. Biol. Cell. 2000; 11: 2085-2102Crossref PubMed Scopus (98) Google Scholar, 14Sacksteder K.A. Jones J.M. South S.T. Li X. Liu Y. Gould S.J. J. Cell Biol. 2000; 148: 931-944Crossref PubMed Scopus (244) Google Scholar), whereas cells of Saccharomyces cerevisiae deleted for either PEX3 or PEX19 appear to lack any type of identifiable peroxisomal structure (15Höhfeld J. Veenhuis M. Kunau W.H. J. Cell Biol. 1991; 114: 1167-1178Crossref PubMed Scopus (175) Google Scholar, 16Götte K. Girzalsky W. Linkert M. Baumgart E. Kammerer S. Kunau W.H. Erdmann R. Mol. Cell. Biol. 1998; 18: 616-628Crossref PubMed Scopus (163) Google Scholar). Functional peroxisomes that were considered to form by de novo peroxisome synthesis were observed upon reintroduction of the PEX3, PEX16, and PEX19 genes into their respective mutant cells (11Matsuzono Y. Kinoshita N. Tamura S. Shimozawa N. Hamasaki M. Ghaedi K. Wanders R.J. Suzuki Y. Kondo N. Fujiki Y. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 2116-2121Crossref PubMed Scopus (189) Google Scholar, 12South S.T. Gould S.J. J. Cell Biol. 1999; 144: 255-266Crossref PubMed Scopus (193) Google Scholar, 14Sacksteder K.A. Jones J.M. South S.T. Li X. Liu Y. Gould S.J. J. Cell Biol. 2000; 148: 931-944Crossref PubMed Scopus (244) Google Scholar, 17South S.T. Sacksteder K.A. Li X. Liu Y. Gould S.J. J. Cell Biol. 2000; 149: 1345-1360Crossref PubMed Scopus (121) Google Scholar, 18South S.T. Baumgart E. Gould S.J. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 12027-12031Crossref PubMed Scopus (50) Google Scholar); however, the ultimate source of these newly made peroxisomes remains undefined. Here, we report the results of studies linking the ER to de novo peroxisome formation in S. cerevisiae and show using in vivo video microscopy that the amino-terminal 46 amino acids of the peroxin Pex3p initiate the formation of a peroxisomal precursor from the ER membrane from which bona fide peroxisomes can form. All experiments were repeated a minimum of three times. The figures present representative images of the individual experiments Yeast Strains, Culture Conditions, and Plasmids—The S. cerevisiae strains used in this study are listed in TABLE ONE. Strains were cultured at 30 °C, unless otherwise indicated. Strains containing plasmids were cultured in synthetic minimal medium. Media components were as follows: YPD, 1% yeast extract, 2% peptone, 2% glucose; YPR, 1% yeast extract, 2% peptone, 2% raffinose; YPBO, 0.3% yeast extract, 0.5% peptone, 0.5% K2HPO4, 0.5% KH2PO4, 0.2% Tween 40, 1% oleic acid; SCIM, 0.67% yeast nitrogen base without amino acids (YNB), 0.5% yeast extract, 0.5% peptone, 0.5% Tween 40, 0.1% glucose, 0.15% oleic acid, 1× complete supplement mixture (CSM) (Bio 101); synthetic minimal medium, 0.67% YNB, 2% glucose, 1× CSM without leucine and uracil; raffinose induction medium (RIM), 0.67% YNB, 0.5% yeast extract, 0.5% peptone, 0.5% Tween 40, 0.1% raffinose, 0.5% oleic acid, 1× CSM; galactose induction medium (GIM), 0.67% YNB, 0.5% yeast extract, 0.5% peptone, 0.5% Tween 40, 2% galactose, 0.5% oleic acid, 1× CSM.TABLE ONES. cerevisiae strains used in this study Strain Genotype Ref. BY4741 MATα, his3Δ1, leu2Δ0, met15Δ0, ura3Δ0 38 BY4742 MATα, his3Δ1, leu2Δ0, lys2Δ0, ura3Δ0 38 pex3Δ MATα, his3Δ1, leu2Δ0, lys2Δ0, ura3Δ0, pex3::KanMX4 38 pex19Δ MATα, his3Δ1, leu2Δ0, lys2Δ0, ura3Δ0, pex19::KanMX4 38 46aa-GFP MATα, his3Δ1, leu2Δ0, met15Δ0, ura3Δ0, pex3::46aa-GFP (HIS5) This study PEX3-GFP MATα, his3Δ1, leu2Δ0, met15Δ0, ura3Δ0, pex3::PEX3-GFP (HIS5) This study GAL1PEX3/POT1-mRFP MATα, his3Δ1, leu2Δ0, lys2Δ0, met15Δ0, ura3Δ0, pex3::GAL1PEX3 (KanMX6), pot1::POT1-mRFP (HIS5) This study GAL1PEX3/FOX2-mRFP-SKL MATα, his3Δ1, leu2Δ0, lys2Δ0, ura3Δ0, pex3::GAL1PEX3 (KanMX6),fox2::FOX2-mRFP-SKL (HIS5) This study GAL1PEX3-mRFP MATα, his3Δ1, leu2Δ0, lys2Δ0, ura3Δ0, pex3::GAL1PEX3 (KanMX6), pex3::PEX3-mRFP (HIS5) This study 46aa-GFP/KAR2-mRFP-HDEL MATα, his3Δ1, leu2Δ0, lys2Δ0, ura3Δ0, pex3::46aa-GFP (HIS5), kar2::KAR2-mRFP-HDEL (HIS5) This study B59P MATα/MATα, his3Δ1/his3Δ1, leu2Δ0/leu2Δ0, met15Δ0/met15Δ0, +/lys2Δ0, ura3Δ0/ura3Δ0, pex3::46aa-GFP (HIS5)/pex3::GAL1PEX3 (KanMX6), pot1::POT1-mRFP (HIS5)/+ This study B523F MATα/MATα, his3Δ1/his3Δ1, leu2Δ0/leu2Δ0, met15Δ0/+, +/lys2Δ0, ura3Δ0/ura3Δ0, pex3::46aa-GFP (HIS5)/pex3::GAL1PEX3 (KanMX6), fox2::FOX2-mRFP-SKL (HIS5)/+ This study B5P3 MATα/MATα, his3Δ1/his3Δ1, leu2Δ0/leu2Δ0, met15Δ0/+, +/lys2Δ0, ura3Δ0/ura3Δ0, pex3::46aa-GFP (HIS5)/pex3::GAL1PEX30-mRFP (HIS5) This study B59P-pex14Δ MATα/MATα, his3Δ1/his3Δ1, leu2Δ0/leu2Δ0, met15Δ0/met15Δ0, +/lys2Δ0, ura3Δ0/ura3Δ0, pex14::URA3/pex14::URA3, pex3::46aa-GFP (HIS5)/pex3::GAL1PEX3 (KanMX6), pot1::POT1-mRFP (HIS5)/+ This study B59P-pex19Δ MATα/MATα, his3Δ1/his3Δ1, leu2Δ0/leu2Δ0, met15Δ0/met15Δ0, +/lys2Δ0, ura3Δ0/ura3Δ0, pex19::URA3/pex19::URA3, pex3::46aa-GFP (HIS5)/pex3::GAL1PEX3 (KanMX6), pot1::POT1-mRFP (HIS5)/+ This study B5P3-pex14Δ MATα/MATα, his3Δ1/his3Δ1, leu2Δ0/leu2Δ0, met15Δ0/+, +/lys2Δ0, ura3Δ0/ura3Δ0, pex14::URA3/pex14::URA3, pex3::46aa-GFP (HIS5)/pex3::GAL1PEX3-mRFP (HIS5) This study B5P3-pex19Δ MATα/MATα, his3Δ1/his3Δ1, leu2Δ0/leu2Δ0, met15Δ0/+, +/lys2Δ0, ura3Δ0/ura3Δ0, pex19::URA3/pex19::URA3, pex3::46aa-GFP (HIS5)/pex3::GAL1PEX3-mRFP (HIS5) This study Open table in a new tab Plasmids pFA6a-kanMX6-PGAL1 (19Longtine M.S. McKenzie A. II I Demarini D.J. Shah N.G. Wach A. Brachat A. Philippsen P. Pringle J.R. Yeast. 1998; 14: 953-961Crossref PubMed Scopus (4193) Google Scholar), pRS315 (20Sikorski R.S. Hieter P. Genetics. 1989; 122: 19-27Crossref PubMed Google Scholar), and pRS406 (21Brachmann C.B. Davies A. Cost G.J. Caputo E. Li J. Hieter P. Boeke J.D. Yeast. 1998; 14: 115-132Crossref PubMed Scopus (2646) Google Scholar) have been described previously. pmRFP-SKL was constructed by replacing the gene for red fluorescent protein in the plasmid pDsRed-PTS1 (22Smith J.J. Marelli M. Christmas R.H. Vizeacoumar F.J. Dilworth D.J. Ideker T. Galitski T. K. Rachubinski R.A. J.D. J. Cell Biol. PubMed Scopus Google Scholar) with the gene monomeric red fluorescent protein R.E. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). and were constructed by replacing the gene for in D.J. A. J.D. J. Cell Biol. 2001; PubMed Scopus Google Scholar) by the genes A. W. M. J. Biochem. 2000; PubMed Scopus (158) Google Scholar) and mRFP, respectively. A containing of of the PEX3 gene was the of pRS315 to the plasmid The plasmids and were constructed by containing of of the PEX3 gene and the amino-terminal amino acids or the amino-terminal 46 amino acids of Pex3p or full-length Pex3p, the of by of the into the of of yeast was used to genes with the and to the of the PEX3 gene by D.J. A. J.D. J. Cell Biol. 2001; PubMed Scopus Google Scholar). were to in synthetic minimal medium and in medium for or for 16 cells in medium were in for 16 and to were on a or on an with a were for microscopy Rachubinski R.A. Mol. Biol. Cell. PubMed Google Scholar) and microscopy Rachubinski R.A. J. Cell Biol. 1997; PubMed Scopus Google Scholar). in in medium and in for 16 were for in vivo video microscopy by of on a with a containing 2% galactose, which was with a and with J.R. J.A. J. Cell Biol. 2001; PubMed Scopus Google Scholar). were at for were using a with a normal 2000; 1: Google Scholar). A was used to for of A of of of were was using a and its was using a was using a and its was using a were three using a to images from were using an that of by an for for of and was by the with The images from were using a These were using was used to fluorescent and to amino acids of Pex3p and to were in and to the J.D. Rachubinski R.A. Yeast. PubMed Scopus Google Scholar) and to peroxisomal V.I. J.J. Veenhuis M. Rachubinski R.A. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar) have been described previously. to S. cerevisiae were obtained from and were used to in and were used to in was as described (22Smith J.J. Marelli M. Christmas R.H. Vizeacoumar F.J. Dilworth D.J. Ideker T. Galitski T. K. Rachubinski R.A. J.D. J. Cell Biol. PubMed Scopus Google Scholar). cell were as described Rachubinski R.A. J. Cell Biol. 1997; PubMed Scopus Google Scholar). in were by Pex3p for Pex3p and the of an and Pex19p early in the biogenesis of peroxisomes in S. cerevisiae as cells lacking either peroxin do not contain peroxisomes, and peroxisomes can be observed to form upon their Pex3p is to be the for Pex19p on the peroxisomal membrane Y. Jones J.M. Gould S.J. J. Cell Biol. PubMed Scopus (175) Google Scholar). This the function of Pex3p in peroxisome biogenesis of that of Pex3p as the protein with which to study the early events of peroxisome biogenesis. to the amino-terminal or 46 amino acids of Pex3p or to full-length Pex3p were the of the PEX3 from plasmid in the BY4741 and in the strains pex3Δ and was into the strains to peroxisomes, and cells were in oleic medium and by microscopy was to target to peroxisomes in BY4741 and pex3Δ cells, as shown by the of and in However, in pex19Δ cells, was to that not with the and do not to peroxisomes, that the formation of peroxisomes a of The localized to the of cells of strains the that BY4741 cells contain peroxisomes. pex3Δ cells were to form peroxisomes, that the for the formation of peroxisomes is not by the amino acids of Pex3p. 46aa-GFP was to peroxisomes in BY4741 was to target to peroxisomes, the peroxisome targeting of Pex3p to amino acids and in pex3Δ and pex19Δ cells, 46aa-GFP localized to an compartment by or two fluorescent These were not peroxisomes, as they not with which to the The of 46aa-GFP to be to peroxisomes in BY4741 cells that contain peroxisomes and to an compartment in pex3Δ and pex19Δ cells that lack peroxisomes that this compartment serve as a preperoxisomal compartment from which peroxisomes could form upon of cells with full-length Pex3p. of 46aa-GFP to the compartment is of with a report that Pex19p is not required to target Pex3p to peroxisomes Y. Jones J.M. Gould S.J. J. Cell Biol. PubMed Scopus (175) Google Scholar). of gene from of Pex3p and the amino-terminal 46 amino acids of Pex3p were observed with from plasmid of oleic cells showed that localized to with the of peroxisomes, whereas localized to an compartment that as or two fluorescent of oleic cells with to the or to the showed that cells peroxisomes both and proteins, as observed for BY4741 cells In cells showed a for both and proteins, as in pex3Δ cells, with the of peroxisomes in both cell The of the was by cells on medium containing oleic as the the of which functional peroxisomes. at a to that of BY4741 cells that Pex3p. pex3Δ cells to or not at that peroxisomal function is in these In peroxisomes of BY4741 cells in oleic medium as in by a membrane and containing a matrix (22Smith J.J. Marelli M. Christmas R.H. Vizeacoumar F.J. Dilworth D.J. Ideker T. Galitski T. K. Rachubinski R.A. J.D. J. Cell Biol. PubMed Scopus Google Scholar, Rachubinski R.A. Mol. Biol. Cell. PubMed Google Scholar, Rachubinski R.A. J. Cell Biol. 1997; PubMed Scopus Google Scholar). In pex3Δ cells and cells identifiable peroxisomes. The of Pex3p a of the cells do not contain peroxisomes we to the subcellular compartment containing the by of with known not with with but showed an with a fluorescent of the In cells, of with also of to the ER compartment Pex3p in BY4741 cells localized to the for peroxisomes. also localized to the but a of was also in the for and localized to the of the to both the and in a to that of with a of and that of found in the these results that the compartment to which is a subdomain of the of in strains Strains of in cells of with 46aa-GFP/KAR2-mRFP-HDEL not 46aa-GFP not Open table in a new tab Peroxisomes from the by the of the compartment be a preperoxisomal the of this compartment upon synthesis of full-length Pex3p, cells were to cells Pex3p the of a and the cells were by The strains also of the of the peroxisomal matrix and or of the were in medium and to medium images were at to both matrix were localized to the and for was synthesis of at in and with the by induction of Pex3p, both and also to the of the B59P showed peroxisomal at but showed characteristic peroxisomes at to is that cells showed peroxisome in for A and of of synthesis of Pex3p In in GIM, the of that galactose the normal induction observed for Pex3p in oleic medium. in vivo video microscopy has a with which to study the of cellular has been used to the de novo formation of ER and Nat. Cell Biol. PubMed Scopus Google Scholar). used in vivo video microscopy to the of the compartment and the formation of peroxisomes. B5P3 and B59P cells were in RIM, to for and an containing oleic and a of and B5P3 cells which the gene for from PEX3 the of the showed the synthesis and import of into and video In B59P cells, which Pex3p from PEX3 the of the showed the import of from the into the compartment and video These results that the amino-terminal 46 amino acids of Pex3p contain sufficient to target to a compartment but to the formation of peroxisomes. Only in the presence of full-length Pex3p, which is to the compartment as the can peroxisomes form. of Pex3p through the ER to peroxisomes has not been observed in cells, perhaps of the of peroxisome division peroxisome de novo formation or the of Pex3p through the ER is that microscopy is to the of the the of the peroxisomal precursor from the ER as of Pex3p of the amino-terminal amino acids for this we have of full-length Pex3p with led to the formation of bona fide peroxisomes of peroxisomal matrix and membrane protein import from the and with for the of the peroxisomal precursor from the ER by of the Pex3p to its 46 amino be that cells and full-length Pex3p to be of peroxisomes However, peroxisomes of matrix and membrane proteins were observed in cells of not the of in these cells, of of newly synthesized Peroxisome from the and and Pex19p are required for peroxisome is the point of of the and matrix protein import M. P. Erdmann R. Girzalsky W. Kiel J.A. Veenhuis M. Kunau W.H. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). Pex19p is required for in targeting to the peroxisomal membrane for peroxisomal membrane proteins K.A. Jones J.M. South S.T. Li X. Liu Y. Gould S.J. J. Cell Biol. 2000; 148: 931-944Crossref PubMed Scopus (244) Google Scholar, Girzalsky W. van Erdmann R. Distel B. J. 2000; PubMed Scopus Google Scholar). what roles and Pex19p have in the of the lacking or Pex19p were in and to GIM, and of cells were at The for and were deleted for either PEX14 or PEX19 showed of with when to GIM, and the synthesis of was However, and was not to both PEX14 and PEX19 are required for the of into peroxisomes. This study that the amino of Pex3p to peroxisomes in cells and a subdomain of the ER in cells lacking peroxisomes. This subdomain of the ER can into functional peroxisomes through the activity of full-length Pex3p. microscopy of mouse dendritic cells has shown that the peroxisomal membrane protein Pex13p can be found in a specialized ER subdomain (10Geuze H.J. Murk J.L. Stroobants A.K. Griffith J.M. Kleijmeer M.J. Koster A.J. Verkleij A.J. Distel B. Tabak H.F. Mol. Biol. Cell. 2003; 14: 2900-2907Crossref PubMed Scopus (148) Google Scholar). this specialized ER subdomain and a structure peroxisomes. These results a peroxisome at the However, a peroxisomal reticulum has not been observed in were to any structure in that to the structure by This is not that that the preperoxisomal of Y. lipolytica have a that not from the of in the cell V.I. Chan H. Rachubinski R.A. J. Cell Biol. 2000; 148: PubMed Scopus Google Scholar). support a for peroxisome that at the of the ER, is to show the of peroxisomes in to the ER in of the import of both peroxisomal membrane and matrix in vivo video we showed the targeting of the peroxisomal membrane protein to that both the and biochemical of a subdomain of the The formation of this compartment was by the of and this compartment was also to import of the matrix protein and the matrix protein this preperoxisomal compartment from the ER remains The targeting of the membrane proteins Pex3p, and Pex16p to peroxisomes was in cells in or S.T. Sacksteder K.A. Li X. Liu Y. Gould S.J. J. Cell Biol. 2000; 149: 1345-1360Crossref PubMed Scopus (121) Google Scholar, T. A. Tabak H.F. Distel B. J. Cell Sci. 2001; 114: PubMed Google Scholar, A.M. S. S. A. K. B. A. M. R. R. Brachat S. S. M. K. A. P. D.J. M. U. J.H. S. P. N. H. H. Liu M. R. P. J.L. M. P. B. B. S. M. J. Y. E. K. H. Boeke J.D. M. Philippsen P. M. PubMed Scopus Google Scholar). However, experiments in H. polymorpha showed that a of peroxisomal proteins was in the ER in cells with brefeldin A (6Salomons F.A. van der Klei I Kram A.M. Harder W. Veenhuis M. FEBS Lett. 1997; 411: 133-139Crossref PubMed Scopus (50) Google Scholar). A role for and in peroxisome formation has to be in S. the ER is also Pex3p have that direct to the ER, or proteins in Pex3p to the of the ER components and not have an on peroxisome biogenesis S.T. Baumgart E. Gould S.J. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 12027-12031Crossref PubMed Scopus (50) Google Scholar). This has been by as that the ER was not in peroxisome biogenesis. However, proteins could the ER mechanism of or experiments at in the import of Pex3p into the ER this Our findings a for and Pex19p in the formation of peroxisomes from the preperoxisomal compartment that are also of matrix protein import from the are with a in which Pex19p to Pex3p to the import of peroxisomal membrane proteins as Y. Jones J.M. Gould S.J. J. Cell Biol. PubMed Scopus (175) Google Scholar). In we show that the peroxisomal integral membrane protein Pex3p through the ER and in the formation of preperoxisomal from this the continued activity of Pex3p, these preperoxisomal can into bona fide peroxisomes the import of peroxisomal matrix and membrane Our findings a direct role for the ER in the de novo formation of peroxisomes. and for and Chan for with with

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.