Rapid cell-surface prion protein conversion revealed using a novel cell system
Prion diseases are fatal neurodegenerative disorders with unique transmissible properties. The infectious and pathological agent is thought to be a misfolded conformer of the prion protein. Little is known about the initial events in prion infection because the infecting prion source has been immuno...
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| Veröffentlicht in: | Nature communications 2011-04, Vol.2 (1), p.281-281, Article 281 |
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| creator | Goold, R. Rabbanian, S. Sutton, L. Andre, R. Arora, P. Moonga, J. Clarke, A.R. Schiavo, G. Jat, P. Collinge, J. Tabrizi, S.J. |
| description | Prion diseases are fatal neurodegenerative disorders with unique transmissible properties. The infectious and pathological agent is thought to be a misfolded conformer of the prion protein. Little is known about the initial events in prion infection because the infecting prion source has been immunologically indistinguishable from normal cellular prion protein (PrP
C
). Here we develop a unique cell system in which epitope-tagged PrP
C
is expressed in a PrP knockdown (KD) neuroblastoma cell line. The tagged PrP
C
, when expressed in our PrP-KD cells, supports prion replication with the production of
bona fide
epitope-tagged infectious misfolded PrP (PrP
Sc
). Using this epitope-tagged PrP
Sc
, we study the earliest events in cellular prion infection and PrP misfolding. We show that prion infection of cells is extremely rapid occurring within 1 min of prion exposure, and we demonstrate that the plasma membrane is the primary site of prion conversion.
The study of prion diseases has been hampered as there is no method to distinguish newly formed abnormal prion protein conformers. Here, the authors describe a method to study newly formed abnormal prion protein and demonstrate that it is produced within 1 minute of cell exposure to prions. |
| doi_str_mv | 10.1038/ncomms1282 |
| format | Article |
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C
). Here we develop a unique cell system in which epitope-tagged PrP
C
is expressed in a PrP knockdown (KD) neuroblastoma cell line. The tagged PrP
C
, when expressed in our PrP-KD cells, supports prion replication with the production of
bona fide
epitope-tagged infectious misfolded PrP (PrP
Sc
). Using this epitope-tagged PrP
Sc
, we study the earliest events in cellular prion infection and PrP misfolding. We show that prion infection of cells is extremely rapid occurring within 1 min of prion exposure, and we demonstrate that the plasma membrane is the primary site of prion conversion.
The study of prion diseases has been hampered as there is no method to distinguish newly formed abnormal prion protein conformers. Here, the authors describe a method to study newly formed abnormal prion protein and demonstrate that it is produced within 1 minute of cell exposure to prions.</description><identifier>ISSN: 2041-1723</identifier><identifier>EISSN: 2041-1723</identifier><identifier>DOI: 10.1038/ncomms1282</identifier><identifier>PMID: 21505437</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/337 ; 631/67 ; 631/80/470/460 ; 692/699/375/365/1937 ; Animals ; Blotting, Western ; Cell Line, Tumor ; Fluorescent Antibody Technique ; Gene Knockdown Techniques ; Humanities and Social Sciences ; Membrane Proteins - chemistry ; Mice ; multidisciplinary ; Prion Diseases - metabolism ; Prions - chemistry ; Prions - genetics ; Protein Folding ; Protein Transport ; RNA Interference ; Science ; Science (multidisciplinary) ; Time Factors</subject><ispartof>Nature communications, 2011-04, Vol.2 (1), p.281-281, Article 281</ispartof><rights>The Author(s) 2011</rights><rights>Copyright Nature Publishing Group Apr 2011</rights><rights>Copyright © 2011, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2011 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c440t-e526d4c47b69314f028b2e781d95c783d9125aa2f6a0853513cd72c6650325bc3</citedby><cites>FETCH-LOGICAL-c440t-e526d4c47b69314f028b2e781d95c783d9125aa2f6a0853513cd72c6650325bc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ncomms1282$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://doi.org/10.1038/ncomms1282$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41096,42165,51551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21505437$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Goold, R.</creatorcontrib><creatorcontrib>Rabbanian, S.</creatorcontrib><creatorcontrib>Sutton, L.</creatorcontrib><creatorcontrib>Andre, R.</creatorcontrib><creatorcontrib>Arora, P.</creatorcontrib><creatorcontrib>Moonga, J.</creatorcontrib><creatorcontrib>Clarke, A.R.</creatorcontrib><creatorcontrib>Schiavo, G.</creatorcontrib><creatorcontrib>Jat, P.</creatorcontrib><creatorcontrib>Collinge, J.</creatorcontrib><creatorcontrib>Tabrizi, S.J.</creatorcontrib><title>Rapid cell-surface prion protein conversion revealed using a novel cell system</title><title>Nature communications</title><addtitle>Nat Commun</addtitle><addtitle>Nat Commun</addtitle><description>Prion diseases are fatal neurodegenerative disorders with unique transmissible properties. The infectious and pathological agent is thought to be a misfolded conformer of the prion protein. Little is known about the initial events in prion infection because the infecting prion source has been immunologically indistinguishable from normal cellular prion protein (PrP
C
). Here we develop a unique cell system in which epitope-tagged PrP
C
is expressed in a PrP knockdown (KD) neuroblastoma cell line. The tagged PrP
C
, when expressed in our PrP-KD cells, supports prion replication with the production of
bona fide
epitope-tagged infectious misfolded PrP (PrP
Sc
). Using this epitope-tagged PrP
Sc
, we study the earliest events in cellular prion infection and PrP misfolding. We show that prion infection of cells is extremely rapid occurring within 1 min of prion exposure, and we demonstrate that the plasma membrane is the primary site of prion conversion.
The study of prion diseases has been hampered as there is no method to distinguish newly formed abnormal prion protein conformers. Here, the authors describe a method to study newly formed abnormal prion protein and demonstrate that it is produced within 1 minute of cell exposure to prions.</description><subject>631/337</subject><subject>631/67</subject><subject>631/80/470/460</subject><subject>692/699/375/365/1937</subject><subject>Animals</subject><subject>Blotting, Western</subject><subject>Cell Line, Tumor</subject><subject>Fluorescent Antibody Technique</subject><subject>Gene Knockdown Techniques</subject><subject>Humanities and Social Sciences</subject><subject>Membrane Proteins - chemistry</subject><subject>Mice</subject><subject>multidisciplinary</subject><subject>Prion Diseases - metabolism</subject><subject>Prions - chemistry</subject><subject>Prions - genetics</subject><subject>Protein Folding</subject><subject>Protein Transport</subject><subject>RNA Interference</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Time Factors</subject><issn>2041-1723</issn><issn>2041-1723</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkV1LwzAUhoMoTnQ3_gAp3ghKNZ9teiPI8AtEQfQ6ZOnp7GiTmbQD_72Zm5uKuUhCznPevIcXoUOCzwlm8sIa17aBUEm30B7FnKQkp2z7x32AhiFMcVysIJLzXTSgRGDBWb6HHp_1rC4TA02Tht5X2kAy87WzcXcd1DYxzs7Bh8WThznoBsqkD7WdJDqxbg7NV3MSPkIH7QHaqXQTYLg699HrzfXL6C59eLq9H109pIZz3KUgaFZyw_NxVjDCK0zlmEIuSVkIk0tWFoQKrWmVaSwFE4SZMqcmywRmVIwN20eXS91ZP26hNGA7rxsVnbfafyina_W7Yus3NXFzxQjmgsgocLIS8O69h9Cptg6LQbQF1wclM8apFNmCPP5DTl3vbZxOFVQUORMMR-h0CRnvQvBQra0QrBY5qU1OET76aX6NfqcSgbMlEGLJTsBvvvxH7hOpKJ2r</recordid><startdate>20110401</startdate><enddate>20110401</enddate><creator>Goold, R.</creator><creator>Rabbanian, S.</creator><creator>Sutton, L.</creator><creator>Andre, R.</creator><creator>Arora, P.</creator><creator>Moonga, J.</creator><creator>Clarke, A.R.</creator><creator>Schiavo, G.</creator><creator>Jat, P.</creator><creator>Collinge, J.</creator><creator>Tabrizi, S.J.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7ST</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</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>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>SOI</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110401</creationdate><title>Rapid cell-surface prion protein conversion revealed using a novel cell system</title><author>Goold, R. ; Rabbanian, S. ; Sutton, L. ; Andre, R. ; Arora, P. ; Moonga, J. ; Clarke, A.R. ; Schiavo, G. ; Jat, P. ; Collinge, J. ; Tabrizi, S.J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-e526d4c47b69314f028b2e781d95c783d9125aa2f6a0853513cd72c6650325bc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>631/337</topic><topic>631/67</topic><topic>631/80/470/460</topic><topic>692/699/375/365/1937</topic><topic>Animals</topic><topic>Blotting, Western</topic><topic>Cell Line, Tumor</topic><topic>Fluorescent Antibody Technique</topic><topic>Gene Knockdown Techniques</topic><topic>Humanities and Social Sciences</topic><topic>Membrane Proteins - chemistry</topic><topic>Mice</topic><topic>multidisciplinary</topic><topic>Prion Diseases - metabolism</topic><topic>Prions - chemistry</topic><topic>Prions - genetics</topic><topic>Protein Folding</topic><topic>Protein Transport</topic><topic>RNA Interference</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Goold, R.</creatorcontrib><creatorcontrib>Rabbanian, S.</creatorcontrib><creatorcontrib>Sutton, L.</creatorcontrib><creatorcontrib>Andre, R.</creatorcontrib><creatorcontrib>Arora, P.</creatorcontrib><creatorcontrib>Moonga, J.</creatorcontrib><creatorcontrib>Clarke, A.R.</creatorcontrib><creatorcontrib>Schiavo, G.</creatorcontrib><creatorcontrib>Jat, P.</creatorcontrib><creatorcontrib>Collinge, J.</creatorcontrib><creatorcontrib>Tabrizi, S.J.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Environment Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Goold, R.</au><au>Rabbanian, S.</au><au>Sutton, L.</au><au>Andre, R.</au><au>Arora, P.</au><au>Moonga, J.</au><au>Clarke, A.R.</au><au>Schiavo, G.</au><au>Jat, P.</au><au>Collinge, J.</au><au>Tabrizi, S.J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rapid cell-surface prion protein conversion revealed using a novel cell system</atitle><jtitle>Nature communications</jtitle><stitle>Nat Commun</stitle><addtitle>Nat Commun</addtitle><date>2011-04-01</date><risdate>2011</risdate><volume>2</volume><issue>1</issue><spage>281</spage><epage>281</epage><pages>281-281</pages><artnum>281</artnum><issn>2041-1723</issn><eissn>2041-1723</eissn><abstract>Prion diseases are fatal neurodegenerative disorders with unique transmissible properties. The infectious and pathological agent is thought to be a misfolded conformer of the prion protein. Little is known about the initial events in prion infection because the infecting prion source has been immunologically indistinguishable from normal cellular prion protein (PrP
C
). Here we develop a unique cell system in which epitope-tagged PrP
C
is expressed in a PrP knockdown (KD) neuroblastoma cell line. The tagged PrP
C
, when expressed in our PrP-KD cells, supports prion replication with the production of
bona fide
epitope-tagged infectious misfolded PrP (PrP
Sc
). Using this epitope-tagged PrP
Sc
, we study the earliest events in cellular prion infection and PrP misfolding. We show that prion infection of cells is extremely rapid occurring within 1 min of prion exposure, and we demonstrate that the plasma membrane is the primary site of prion conversion.
The study of prion diseases has been hampered as there is no method to distinguish newly formed abnormal prion protein conformers. Here, the authors describe a method to study newly formed abnormal prion protein and demonstrate that it is produced within 1 minute of cell exposure to prions.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>21505437</pmid><doi>10.1038/ncomms1282</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Nature communications, 2011-04, Vol.2 (1), p.281-281, Article 281 |
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| language | eng |
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| subjects | 631/337 631/67 631/80/470/460 692/699/375/365/1937 Animals Blotting, Western Cell Line, Tumor Fluorescent Antibody Technique Gene Knockdown Techniques Humanities and Social Sciences Membrane Proteins - chemistry Mice multidisciplinary Prion Diseases - metabolism Prions - chemistry Prions - genetics Protein Folding Protein Transport RNA Interference Science Science (multidisciplinary) Time Factors |
| title | Rapid cell-surface prion protein conversion revealed using a novel cell system |
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