Pex3p-dependent peroxisomal biogenesis initiates in the endoplasmic reticulum of human fibroblasts
The mechanisms of peroxisomal biogenesis remain incompletely understood, specially regarding the role of the endoplasmic reticulum (ER) in human cells, where genetic disorders of peroxisome biogenesis lead to Zellweger syndrome (ZS). The Pex3p peroxisomal membrane protein (PMP) required for early st...
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Veröffentlicht in: | Journal of cellular biochemistry 2009-08, Vol.107 (6), p.1083-1096 |
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container_title | Journal of cellular biochemistry |
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creator | Toro, Andrés A. Araya, Claudia A. Córdova, Gonzalo J. Arredondo, Cristian A. Cárdenas, Hugo G. Moreno, Regina E. Venegas, Alejandro Koenig, Cecilia S. Cancino, Jorge Gonzalez, Alfonso Santos, Manuel J. |
description | The mechanisms of peroxisomal biogenesis remain incompletely understood, specially regarding the role of the endoplasmic reticulum (ER) in human cells, where genetic disorders of peroxisome biogenesis lead to Zellweger syndrome (ZS). The Pex3p peroxisomal membrane protein (PMP) required for early steps of peroxisome biogenesis has been detected in the ER in yeast but not in mammalian cells. Here, we show that Pex3p‐GFP expressed in a new ZS cell line (MR), which lacks peroxisomes due to a mutation in the PEX3 gene, localizes first in the ER and subsequently in newly formed peroxisomes. Pex3p bearing an artificial N‐glycosylation site shows an electrophoretic shift indicative of ER targeting while en route to preformed peroxisomes in normal fibroblast. A signal peptide that forces its entry into the ER does not eliminate its capability to drive peroxisome biogenesis in ZS cells. Thus, Pex3p is able to drive peroxisome biogenesis from the ER and its ER pathway is not privative of ZS cells. Cross‐expression experiments of Pex3p in GM623 cells lacking Pex16p or Pex16p in MR cells lacking Pex3p, showed evidence that Pex3p requires Pex16p for ER location but is dispensable for the ER location of Pex16p. These results indicate that Pex3p follows the ER‐to‐peroxisomal route in mammalian cells and provides new clues to understand its function. J. Cell. Biochem. 107: 1083–1096, 2009. © 2009 Wiley‐Liss, Inc. |
doi_str_mv | 10.1002/jcb.22210 |
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The Pex3p peroxisomal membrane protein (PMP) required for early steps of peroxisome biogenesis has been detected in the ER in yeast but not in mammalian cells. Here, we show that Pex3p‐GFP expressed in a new ZS cell line (MR), which lacks peroxisomes due to a mutation in the PEX3 gene, localizes first in the ER and subsequently in newly formed peroxisomes. Pex3p bearing an artificial N‐glycosylation site shows an electrophoretic shift indicative of ER targeting while en route to preformed peroxisomes in normal fibroblast. A signal peptide that forces its entry into the ER does not eliminate its capability to drive peroxisome biogenesis in ZS cells. Thus, Pex3p is able to drive peroxisome biogenesis from the ER and its ER pathway is not privative of ZS cells. Cross‐expression experiments of Pex3p in GM623 cells lacking Pex16p or Pex16p in MR cells lacking Pex3p, showed evidence that Pex3p requires Pex16p for ER location but is dispensable for the ER location of Pex16p. These results indicate that Pex3p follows the ER‐to‐peroxisomal route in mammalian cells and provides new clues to understand its function. J. Cell. Biochem. 107: 1083–1096, 2009. © 2009 Wiley‐Liss, Inc.</description><identifier>ISSN: 0730-2312</identifier><identifier>EISSN: 1097-4644</identifier><identifier>DOI: 10.1002/jcb.22210</identifier><identifier>PMID: 19479899</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Acyltransferases ; biogenesis ; Case-Control Studies ; Catalase ; endoplasmic reticulum ; Endoplasmic Reticulum - enzymology ; Endoplasmic Reticulum - metabolism ; Fibroblasts - cytology ; Humans ; Lipoproteins - genetics ; Lipoproteins - metabolism ; Lipoproteins - physiology ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Membrane Proteins - physiology ; Mutation ; Peroxins ; peroxisome ; Peroxisomes - metabolism ; Protein Transport ; Zellweger Syndrome</subject><ispartof>Journal of cellular biochemistry, 2009-08, Vol.107 (6), p.1083-1096</ispartof><rights>Copyright © 2009 Wiley‐Liss, Inc.</rights><rights>(c) 2009 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4280-917d69b415e34d4b4e917c36338be34ee33862d05c6c15cd46e48c56e69a667c3</citedby><cites>FETCH-LOGICAL-c4280-917d69b415e34d4b4e917c36338be34ee33862d05c6c15cd46e48c56e69a667c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcb.22210$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcb.22210$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19479899$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Toro, Andrés A.</creatorcontrib><creatorcontrib>Araya, Claudia A.</creatorcontrib><creatorcontrib>Córdova, Gonzalo J.</creatorcontrib><creatorcontrib>Arredondo, Cristian A.</creatorcontrib><creatorcontrib>Cárdenas, Hugo G.</creatorcontrib><creatorcontrib>Moreno, Regina E.</creatorcontrib><creatorcontrib>Venegas, Alejandro</creatorcontrib><creatorcontrib>Koenig, Cecilia S.</creatorcontrib><creatorcontrib>Cancino, Jorge</creatorcontrib><creatorcontrib>Gonzalez, Alfonso</creatorcontrib><creatorcontrib>Santos, Manuel J.</creatorcontrib><title>Pex3p-dependent peroxisomal biogenesis initiates in the endoplasmic reticulum of human fibroblasts</title><title>Journal of cellular biochemistry</title><addtitle>J. Cell. Biochem</addtitle><description>The mechanisms of peroxisomal biogenesis remain incompletely understood, specially regarding the role of the endoplasmic reticulum (ER) in human cells, where genetic disorders of peroxisome biogenesis lead to Zellweger syndrome (ZS). The Pex3p peroxisomal membrane protein (PMP) required for early steps of peroxisome biogenesis has been detected in the ER in yeast but not in mammalian cells. Here, we show that Pex3p‐GFP expressed in a new ZS cell line (MR), which lacks peroxisomes due to a mutation in the PEX3 gene, localizes first in the ER and subsequently in newly formed peroxisomes. Pex3p bearing an artificial N‐glycosylation site shows an electrophoretic shift indicative of ER targeting while en route to preformed peroxisomes in normal fibroblast. A signal peptide that forces its entry into the ER does not eliminate its capability to drive peroxisome biogenesis in ZS cells. Thus, Pex3p is able to drive peroxisome biogenesis from the ER and its ER pathway is not privative of ZS cells. Cross‐expression experiments of Pex3p in GM623 cells lacking Pex16p or Pex16p in MR cells lacking Pex3p, showed evidence that Pex3p requires Pex16p for ER location but is dispensable for the ER location of Pex16p. These results indicate that Pex3p follows the ER‐to‐peroxisomal route in mammalian cells and provides new clues to understand its function. J. Cell. Biochem. 107: 1083–1096, 2009. © 2009 Wiley‐Liss, Inc.</description><subject>Acyltransferases</subject><subject>biogenesis</subject><subject>Case-Control Studies</subject><subject>Catalase</subject><subject>endoplasmic reticulum</subject><subject>Endoplasmic Reticulum - enzymology</subject><subject>Endoplasmic Reticulum - metabolism</subject><subject>Fibroblasts - cytology</subject><subject>Humans</subject><subject>Lipoproteins - genetics</subject><subject>Lipoproteins - metabolism</subject><subject>Lipoproteins - physiology</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Membrane Proteins - physiology</subject><subject>Mutation</subject><subject>Peroxins</subject><subject>peroxisome</subject><subject>Peroxisomes - metabolism</subject><subject>Protein Transport</subject><subject>Zellweger Syndrome</subject><issn>0730-2312</issn><issn>1097-4644</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEtP3DAURq0KVAbogj-AvKu6CPgVZ7ykozK8WrroQ5qNZTt3imkSBzsRw7_HMAOsWN1P9577LQ5CB5QcUULY8a2zR4wxSj6gCSWqKoQUYgtNSMVJwThlO2g3pVtCiFKcfUQ7VIlKTZWaIPsTVrwvauihq6EbcA8xrHwKrWmw9eEfdJB8wr7zgzcDPCU83ADOeOgbk1rvcITBu7EZWxyW-GZsTYeX3sZg831I-2h7aZoEnzZzD_0-_fZrdlZcXc_PZydXhRNsSgpFq1oqK2gJXNTCCsgbxyXnU5s3ADlIVpPSSUdLVwsJYupKCVIZKTO5hz6ve_sY7kZIg259ctA0poMwJl1xXmYhlGfyy5p0MaQUYan76FsTHzQl-smozkb1s9HMHm5aR9tC_UZuFGbgeA3c-wYe3m_SF7OvL5XF-sOnAVavHyb-17LiVan__pjrxSVb8D-zhf7OHwGd0Y_f</recordid><startdate>20090815</startdate><enddate>20090815</enddate><creator>Toro, Andrés A.</creator><creator>Araya, Claudia A.</creator><creator>Córdova, Gonzalo J.</creator><creator>Arredondo, Cristian A.</creator><creator>Cárdenas, Hugo G.</creator><creator>Moreno, Regina E.</creator><creator>Venegas, Alejandro</creator><creator>Koenig, Cecilia S.</creator><creator>Cancino, Jorge</creator><creator>Gonzalez, Alfonso</creator><creator>Santos, Manuel J.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20090815</creationdate><title>Pex3p-dependent peroxisomal biogenesis initiates in the endoplasmic reticulum of human fibroblasts</title><author>Toro, Andrés A. ; Araya, Claudia A. ; Córdova, Gonzalo J. ; Arredondo, Cristian A. ; Cárdenas, Hugo G. ; Moreno, Regina E. ; Venegas, Alejandro ; Koenig, Cecilia S. ; Cancino, Jorge ; Gonzalez, Alfonso ; Santos, Manuel J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4280-917d69b415e34d4b4e917c36338be34ee33862d05c6c15cd46e48c56e69a667c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Acyltransferases</topic><topic>biogenesis</topic><topic>Case-Control Studies</topic><topic>Catalase</topic><topic>endoplasmic reticulum</topic><topic>Endoplasmic Reticulum - enzymology</topic><topic>Endoplasmic Reticulum - metabolism</topic><topic>Fibroblasts - cytology</topic><topic>Humans</topic><topic>Lipoproteins - genetics</topic><topic>Lipoproteins - metabolism</topic><topic>Lipoproteins - physiology</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Membrane Proteins - physiology</topic><topic>Mutation</topic><topic>Peroxins</topic><topic>peroxisome</topic><topic>Peroxisomes - metabolism</topic><topic>Protein Transport</topic><topic>Zellweger Syndrome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Toro, Andrés A.</creatorcontrib><creatorcontrib>Araya, Claudia A.</creatorcontrib><creatorcontrib>Córdova, Gonzalo J.</creatorcontrib><creatorcontrib>Arredondo, Cristian A.</creatorcontrib><creatorcontrib>Cárdenas, Hugo G.</creatorcontrib><creatorcontrib>Moreno, Regina E.</creatorcontrib><creatorcontrib>Venegas, Alejandro</creatorcontrib><creatorcontrib>Koenig, Cecilia S.</creatorcontrib><creatorcontrib>Cancino, Jorge</creatorcontrib><creatorcontrib>Gonzalez, Alfonso</creatorcontrib><creatorcontrib>Santos, Manuel J.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cellular biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Toro, Andrés A.</au><au>Araya, Claudia A.</au><au>Córdova, Gonzalo J.</au><au>Arredondo, Cristian A.</au><au>Cárdenas, Hugo G.</au><au>Moreno, Regina E.</au><au>Venegas, Alejandro</au><au>Koenig, Cecilia S.</au><au>Cancino, Jorge</au><au>Gonzalez, Alfonso</au><au>Santos, Manuel J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pex3p-dependent peroxisomal biogenesis initiates in the endoplasmic reticulum of human fibroblasts</atitle><jtitle>Journal of cellular biochemistry</jtitle><addtitle>J. Cell. Biochem</addtitle><date>2009-08-15</date><risdate>2009</risdate><volume>107</volume><issue>6</issue><spage>1083</spage><epage>1096</epage><pages>1083-1096</pages><issn>0730-2312</issn><eissn>1097-4644</eissn><abstract>The mechanisms of peroxisomal biogenesis remain incompletely understood, specially regarding the role of the endoplasmic reticulum (ER) in human cells, where genetic disorders of peroxisome biogenesis lead to Zellweger syndrome (ZS). The Pex3p peroxisomal membrane protein (PMP) required for early steps of peroxisome biogenesis has been detected in the ER in yeast but not in mammalian cells. Here, we show that Pex3p‐GFP expressed in a new ZS cell line (MR), which lacks peroxisomes due to a mutation in the PEX3 gene, localizes first in the ER and subsequently in newly formed peroxisomes. Pex3p bearing an artificial N‐glycosylation site shows an electrophoretic shift indicative of ER targeting while en route to preformed peroxisomes in normal fibroblast. A signal peptide that forces its entry into the ER does not eliminate its capability to drive peroxisome biogenesis in ZS cells. Thus, Pex3p is able to drive peroxisome biogenesis from the ER and its ER pathway is not privative of ZS cells. Cross‐expression experiments of Pex3p in GM623 cells lacking Pex16p or Pex16p in MR cells lacking Pex3p, showed evidence that Pex3p requires Pex16p for ER location but is dispensable for the ER location of Pex16p. These results indicate that Pex3p follows the ER‐to‐peroxisomal route in mammalian cells and provides new clues to understand its function. J. Cell. Biochem. 107: 1083–1096, 2009. © 2009 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>19479899</pmid><doi>10.1002/jcb.22210</doi><tpages>14</tpages></addata></record> |
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subjects | Acyltransferases biogenesis Case-Control Studies Catalase endoplasmic reticulum Endoplasmic Reticulum - enzymology Endoplasmic Reticulum - metabolism Fibroblasts - cytology Humans Lipoproteins - genetics Lipoproteins - metabolism Lipoproteins - physiology Membrane Proteins - genetics Membrane Proteins - metabolism Membrane Proteins - physiology Mutation Peroxins peroxisome Peroxisomes - metabolism Protein Transport Zellweger Syndrome |
title | Pex3p-dependent peroxisomal biogenesis initiates in the endoplasmic reticulum of human fibroblasts |
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