β-Amyloid precursor protein does not possess ferroxidase activity but does stabilize the cell surface ferrous iron exporter ferroportin
Ceruloplasmin is a ferroxidase that interacts with ferroportin to export cellular iron, but is not expressed in neurons. We recently reported that the amyloid precursor protein (APP) is the analogous iron-exporting chaperone for neurons and other cells. The ferroxidase activity of APP has since been...
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| Veröffentlicht in: | PloS one 2014-12, Vol.9 (12), p.e114174-e114174 |
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| creator | Wong, Bruce X Tsatsanis, Andrew Lim, Linh Q Adlard, Paul A Bush, Ashley I Duce, James A |
| description | Ceruloplasmin is a ferroxidase that interacts with ferroportin to export cellular iron, but is not expressed in neurons. We recently reported that the amyloid precursor protein (APP) is the analogous iron-exporting chaperone for neurons and other cells. The ferroxidase activity of APP has since been called into question. Using a triplex Fe2+ oxidation assay, we analyzed the activity of a soluble form of APP (sAPPα) within a buffer of physiological pH and anionic charge, and determined that iron oxidation originated from phosphate. Using various techniques such as flow-cytometry to measure surface presented proteins, we confirmed that endogenous APP is essential for ferroportin persistence on the neuronal surface. Therefore, despite lacking ferroxidase activity, APP still supports iron export from neurons. |
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We recently reported that the amyloid precursor protein (APP) is the analogous iron-exporting chaperone for neurons and other cells. The ferroxidase activity of APP has since been called into question. Using a triplex Fe2+ oxidation assay, we analyzed the activity of a soluble form of APP (sAPPα) within a buffer of physiological pH and anionic charge, and determined that iron oxidation originated from phosphate. Using various techniques such as flow-cytometry to measure surface presented proteins, we confirmed that endogenous APP is essential for ferroportin persistence on the neuronal surface. Therefore, despite lacking ferroxidase activity, APP still supports iron export from neurons.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0114174</identifier><identifier>PMID: 25464026</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alzheimer's disease ; Amyloid beta-Protein Precursor - metabolism ; Amyloid precursor protein ; Animals ; Biology and Life Sciences ; Brain ; Cation Transport Proteins - metabolism ; Cell surface ; Cellular biology ; Ceruloplasmin ; Ceruloplasmin - metabolism ; Cytometry ; Disease ; Exports ; Ferroxidase ; HEK293 Cells ; Humans ; Iron ; Medicine and Health Sciences ; Mental health ; Mice ; Neurons ; Neurosciences ; Oxidation ; Oxidation-Reduction ; Oxidative stress ; Pathology ; Precursors ; Proteins ; β-Amyloid</subject><ispartof>PloS one, 2014-12, Vol.9 (12), p.e114174-e114174</ispartof><rights>2014 Wong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Wong et al 2014 Wong et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-454eba5c5d5005ede2affe235f43ca0681918be5732204fe05a9c7755bdf3aa03</citedby><cites>FETCH-LOGICAL-c526t-454eba5c5d5005ede2affe235f43ca0681918be5732204fe05a9c7755bdf3aa03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252103/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252103/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25464026$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wong, Bruce X</creatorcontrib><creatorcontrib>Tsatsanis, Andrew</creatorcontrib><creatorcontrib>Lim, Linh Q</creatorcontrib><creatorcontrib>Adlard, Paul A</creatorcontrib><creatorcontrib>Bush, Ashley I</creatorcontrib><creatorcontrib>Duce, James A</creatorcontrib><title>β-Amyloid precursor protein does not possess ferroxidase activity but does stabilize the cell surface ferrous iron exporter ferroportin</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Ceruloplasmin is a ferroxidase that interacts with ferroportin to export cellular iron, but is not expressed in neurons. 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Therefore, despite lacking ferroxidase activity, APP still supports iron export from neurons.</description><subject>Alzheimer's disease</subject><subject>Amyloid beta-Protein Precursor - metabolism</subject><subject>Amyloid precursor protein</subject><subject>Animals</subject><subject>Biology and Life Sciences</subject><subject>Brain</subject><subject>Cation Transport Proteins - metabolism</subject><subject>Cell surface</subject><subject>Cellular biology</subject><subject>Ceruloplasmin</subject><subject>Ceruloplasmin - metabolism</subject><subject>Cytometry</subject><subject>Disease</subject><subject>Exports</subject><subject>Ferroxidase</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Iron</subject><subject>Medicine and Health Sciences</subject><subject>Mental health</subject><subject>Mice</subject><subject>Neurons</subject><subject>Neurosciences</subject><subject>Oxidation</subject><subject>Oxidation-Reduction</subject><subject>Oxidative stress</subject><subject>Pathology</subject><subject>Precursors</subject><subject>Proteins</subject><subject>β-Amyloid</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptUstuFDEQHCEQCYE_QGCJC5dZ_J6dC1IU8YgUiQucrR5PO_FqdjzYnijLF_A9fAjfhJfZRAni5Fa7qlzdrqp6yeiKiYa924Q5jjCspjDiijImWSMfVcesFbzWnIrH9-qj6llKG0qVWGv9tDriSmpJuT6ufv7-VZ9ud0PwPZki2jmmEEsVMvqR9AETGUMmU0gJUyIOYww3voeEBGz21z7vSDfnBZkydH7wP5DkKyQWh4GkOTqwuBDnRHwMI8GbKcSMcenuaz8-r544GBK-OJwn1bePH76efa4vvnw6Pzu9qK3iOtdSSexAWdWrMg72yME55EI5KSxQvWYtW3eoGsE5lQ6pgtY2jVJd7wQAFSfV60V3GkIyhyUmwzRvVdsIqgvifEH0ATZmin4LcWcCePO3EeKlgeLYDmiUppZRVky1WkrqWtFrKXRDrVVQjBat94fX5m6LvcUxRxgeiD68Gf2VuQzXRnLFGRVF4O1BIIbvM6Zstj7tNwsjln0W30Lyhsp2XaBv_oH-fzq5oGwsfxrR3Zlh1OyDdcsy-2CZQ7AK7dX9Qe5It0kSfwAbGtAm</recordid><startdate>20141202</startdate><enddate>20141202</enddate><creator>Wong, Bruce X</creator><creator>Tsatsanis, Andrew</creator><creator>Lim, Linh Q</creator><creator>Adlard, Paul A</creator><creator>Bush, Ashley I</creator><creator>Duce, James A</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20141202</creationdate><title>β-Amyloid precursor protein does not possess ferroxidase activity but does stabilize the cell surface ferrous iron exporter ferroportin</title><author>Wong, Bruce X ; Tsatsanis, Andrew ; Lim, Linh Q ; Adlard, Paul A ; Bush, Ashley I ; Duce, James A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-454eba5c5d5005ede2affe235f43ca0681918be5732204fe05a9c7755bdf3aa03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Alzheimer's disease</topic><topic>Amyloid beta-Protein Precursor - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wong, Bruce X</au><au>Tsatsanis, Andrew</au><au>Lim, Linh Q</au><au>Adlard, Paul A</au><au>Bush, Ashley I</au><au>Duce, James A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>β-Amyloid precursor protein does not possess ferroxidase activity but does stabilize the cell surface ferrous iron exporter ferroportin</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-12-02</date><risdate>2014</risdate><volume>9</volume><issue>12</issue><spage>e114174</spage><epage>e114174</epage><pages>e114174-e114174</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Ceruloplasmin is a ferroxidase that interacts with ferroportin to export cellular iron, but is not expressed in neurons. We recently reported that the amyloid precursor protein (APP) is the analogous iron-exporting chaperone for neurons and other cells. The ferroxidase activity of APP has since been called into question. Using a triplex Fe2+ oxidation assay, we analyzed the activity of a soluble form of APP (sAPPα) within a buffer of physiological pH and anionic charge, and determined that iron oxidation originated from phosphate. Using various techniques such as flow-cytometry to measure surface presented proteins, we confirmed that endogenous APP is essential for ferroportin persistence on the neuronal surface. Therefore, despite lacking ferroxidase activity, APP still supports iron export from neurons.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25464026</pmid><doi>10.1371/journal.pone.0114174</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Alzheimer's disease Amyloid beta-Protein Precursor - metabolism Amyloid precursor protein Animals Biology and Life Sciences Brain Cation Transport Proteins - metabolism Cell surface Cellular biology Ceruloplasmin Ceruloplasmin - metabolism Cytometry Disease Exports Ferroxidase HEK293 Cells Humans Iron Medicine and Health Sciences Mental health Mice Neurons Neurosciences Oxidation Oxidation-Reduction Oxidative stress Pathology Precursors Proteins β-Amyloid |
| title | β-Amyloid precursor protein does not possess ferroxidase activity but does stabilize the cell surface ferrous iron exporter ferroportin |
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