Intercellular propagated misfolding of wild-type Cu/Zn superoxide dismutase occurs via exosome-dependent and -independent mechanisms
Identifieur interne : 000A27 ( Main/Exploration ); précédent : 000A26; suivant : 000A28Intercellular propagated misfolding of wild-type Cu/Zn superoxide dismutase occurs via exosome-dependent and -independent mechanisms
Auteurs : Leslie I. Grad [Canada] ; Justin J. Yerbury [Australie] ; Bradley J. Turner ; William C. Guest [Canada] ; Edward Pokrishevsky [Canada] ; Megan A. O Eill [Canada] ; Anat Yanai [Canada] ; Judith M. Silverman [Canada] ; Rafaa Zeineddine [Australie] ; Lisa Corcoran [Australie] ; Janet R. Kumita [Royaume-Uni] ; Leila M. Luheshi [Royaume-Uni] ; Masoud Yousefi [Canada] ; Bradley M. Coleman [Australie] ; Andrew F. Hill [Australie] ; Steven S. Plotkin [Canada] ; Ian R. Mackenzie [Canada] ; Neil R. Cashman [Canada]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2014.
Abstract
Amyotrophic lateral sclerosis (ALS), an incurable motor neuron disease, is associated with mutation and misfolding of the Cu/Zn superoxide dismutase (SOD1) protein. Prior studies found that mutant misfolded SOD1 can convert wild-type (WT) SOD1 to a misfolded form inside living cells in a prion-like fashion. We now report that misfolded WT SOD1 can be transmitted from cell to cell, and that propagated protein misfolding can be perpetuated. Misfolded SOD1 transmission between cells can be mediated through release and uptake of protein aggregates or via small membrane-bounded transport vesicles called exosomes. These mechanisms may help explain why sporadic ALS, without a known genetic cause, can spread systematically from region to region in a progressive manner.
Url:
DOI: 10.1073/pnas.1312245111
PubMed: 24550511
PubMed Central: 3948312
Affiliations:
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Kumita</name><affiliation wicri:level="1"><nlm:aff id="aff6">Department of Chemistry,<institution>University of Cambridge</institution>, Cambridge CB2 1EW,<country>United Kingdom</country>;</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Luheshi, Leila M" sort="Luheshi, Leila M" uniqKey="Luheshi L" first="Leila M." last="Luheshi">Leila M. Luheshi</name><affiliation wicri:level="1"><nlm:aff id="aff6">Department of Chemistry,<institution>University of Cambridge</institution>, Cambridge CB2 1EW,<country>United Kingdom</country>;</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yousefi, Masoud" sort="Yousefi, Masoud" uniqKey="Yousefi M" first="Masoud" last="Yousefi">Masoud Yousefi</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicine (Neurology), University of British Columbia and Vancouver Coastal Health Research Institute, Brain Research Centre, Vancouver, BC,<country>Canada</country> V6T 2B5;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Coleman, Bradley M" sort="Coleman, Bradley M" uniqKey="Coleman B" first="Bradley M." last="Coleman">Bradley M. Coleman</name><affiliation wicri:level="1"><nlm:aff id="aff5">Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute,<institution>University of Melbourne</institution>, Parkville, VIC 3010,<country>Australia</country>;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hill, Andrew F" sort="Hill, Andrew F" uniqKey="Hill A" first="Andrew F." last="Hill">Andrew F. 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Grad</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicine (Neurology), University of British Columbia and Vancouver Coastal Health Research Institute, Brain Research Centre, Vancouver, BC,<country>Canada</country> V6T 2B5;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yerbury, Justin J" sort="Yerbury, Justin J" uniqKey="Yerbury J" first="Justin J." last="Yerbury">Justin J. Yerbury</name><affiliation wicri:level="1"><nlm:aff id="aff3">Illawarra Health and Medical Research Institute,<institution>University of Wollongong</institution>, Wollongong, NSW 2522,<country>Australia</country>;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Turner, Bradley J" sort="Turner, Bradley J" uniqKey="Turner B" first="Bradley J." last="Turner">Bradley J. Turner</name><affiliation><nlm:aff wicri:cut=" and" id="aff4">Florey Institute of Neuroscience and Mental Health</nlm:aff></affiliation></author><author><name sortKey="Guest, William C" sort="Guest, William C" uniqKey="Guest W" first="William C." last="Guest">William C. Guest</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicine (Neurology), University of British Columbia and Vancouver Coastal Health Research Institute, Brain Research Centre, Vancouver, BC,<country>Canada</country> V6T 2B5;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Pokrishevsky, Edward" sort="Pokrishevsky, Edward" uniqKey="Pokrishevsky E" first="Edward" last="Pokrishevsky">Edward Pokrishevsky</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicine (Neurology), University of British Columbia and Vancouver Coastal Health Research Institute, Brain Research Centre, Vancouver, BC,<country>Canada</country> V6T 2B5;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="O Eill, Megan A" sort="O Eill, Megan A" uniqKey="O Eill M" first="Megan A." last="O Eill">Megan A. O Eill</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicine (Neurology), University of British Columbia and Vancouver Coastal Health Research Institute, Brain Research Centre, Vancouver, BC,<country>Canada</country> V6T 2B5;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yanai, Anat" sort="Yanai, Anat" uniqKey="Yanai A" first="Anat" last="Yanai">Anat Yanai</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicine (Neurology), University of British Columbia and Vancouver Coastal Health Research Institute, Brain Research Centre, Vancouver, BC,<country>Canada</country> V6T 2B5;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Silverman, Judith M" sort="Silverman, Judith M" uniqKey="Silverman J" first="Judith M." last="Silverman">Judith M. Silverman</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicine (Neurology), University of British Columbia and Vancouver Coastal Health Research Institute, Brain Research Centre, Vancouver, BC,<country>Canada</country> V6T 2B5;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zeineddine, Rafaa" sort="Zeineddine, Rafaa" uniqKey="Zeineddine R" first="Rafaa" last="Zeineddine">Rafaa Zeineddine</name><affiliation wicri:level="1"><nlm:aff id="aff3">Illawarra Health and Medical Research Institute,<institution>University of Wollongong</institution>, Wollongong, NSW 2522,<country>Australia</country>;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Corcoran, Lisa" sort="Corcoran, Lisa" uniqKey="Corcoran L" first="Lisa" last="Corcoran">Lisa Corcoran</name><affiliation wicri:level="1"><nlm:aff id="aff3">Illawarra Health and Medical Research Institute,<institution>University of Wollongong</institution>, Wollongong, NSW 2522,<country>Australia</country>;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kumita, Janet R" sort="Kumita, Janet R" uniqKey="Kumita J" first="Janet R." last="Kumita">Janet R. Kumita</name><affiliation wicri:level="1"><nlm:aff id="aff6">Department of Chemistry,<institution>University of Cambridge</institution>, Cambridge CB2 1EW,<country>United Kingdom</country>;</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Luheshi, Leila M" sort="Luheshi, Leila M" uniqKey="Luheshi L" first="Leila M." last="Luheshi">Leila M. Luheshi</name><affiliation wicri:level="1"><nlm:aff id="aff6">Department of Chemistry,<institution>University of Cambridge</institution>, Cambridge CB2 1EW,<country>United Kingdom</country>;</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yousefi, Masoud" sort="Yousefi, Masoud" uniqKey="Yousefi M" first="Masoud" last="Yousefi">Masoud Yousefi</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicine (Neurology), University of British Columbia and Vancouver Coastal Health Research Institute, Brain Research Centre, Vancouver, BC,<country>Canada</country> V6T 2B5;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Coleman, Bradley M" sort="Coleman, Bradley M" uniqKey="Coleman B" first="Bradley M." last="Coleman">Bradley M. Coleman</name><affiliation wicri:level="1"><nlm:aff id="aff5">Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute,<institution>University of Melbourne</institution>, Parkville, VIC 3010,<country>Australia</country>;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hill, Andrew F" sort="Hill, Andrew F" uniqKey="Hill A" first="Andrew F." last="Hill">Andrew F. Hill</name><affiliation wicri:level="1"><nlm:aff id="aff5">Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute,<institution>University of Melbourne</institution>, Parkville, VIC 3010,<country>Australia</country>;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Plotkin, Steven S" sort="Plotkin, Steven S" uniqKey="Plotkin S" first="Steven S." last="Plotkin">Steven S. Plotkin</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff2">Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada V6T 1Z1</nlm:aff><country>Canada</country><wicri:regionArea>Department of Physics and Astronomy, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Mackenzie, Ian R" sort="Mackenzie, Ian R" uniqKey="Mackenzie I" first="Ian R." last="Mackenzie">Ian R. Mackenzie</name><affiliation wicri:level="1"><nlm:aff id="aff7">Department of Pathology and Laboratory Medicine,<institution>University of British Columbia</institution>, Vancouver, BC,<country>Canada</country> V5Z 1M9</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cashman, Neil R" sort="Cashman, Neil R" uniqKey="Cashman N" first="Neil R." last="Cashman">Neil R. Cashman</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Medicine (Neurology), University of British Columbia and Vancouver Coastal Health Research Institute, Brain Research Centre, Vancouver, BC,<country>Canada</country> V6T 2B5;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Significance</title><p>Amyotrophic lateral sclerosis (ALS), an incurable motor neuron disease, is associated with mutation and misfolding of the Cu/Zn superoxide dismutase (SOD1) protein. Prior studies found that mutant misfolded SOD1 can convert wild-type (WT) SOD1 to a misfolded form inside living cells in a prion-like fashion. We now report that misfolded WT SOD1 can be transmitted from cell to cell, and that propagated protein misfolding can be perpetuated. Misfolded SOD1 transmission between cells can be mediated through release and uptake of protein aggregates or via small membrane-bounded transport vesicles called exosomes. These mechanisms may help explain why sporadic ALS, without a known genetic cause, can spread systematically from region to region in a progressive manner.</p></div></front></TEI><affiliations><list><country><li>Australie</li><li>Canada</li><li>Royaume-Uni</li></country></list><tree><noCountry><name sortKey="Turner, Bradley J" sort="Turner, Bradley J" uniqKey="Turner B" first="Bradley J." last="Turner">Bradley J. Turner</name></noCountry><country name="Canada"><noRegion><name sortKey="Grad, Leslie I" sort="Grad, Leslie I" uniqKey="Grad L" first="Leslie I." last="Grad">Leslie I. Grad</name></noRegion><name sortKey="Cashman, Neil R" sort="Cashman, Neil R" uniqKey="Cashman N" first="Neil R." last="Cashman">Neil R. Cashman</name><name sortKey="Guest, William C" sort="Guest, William C" uniqKey="Guest W" first="William C." last="Guest">William C. Guest</name><name sortKey="Mackenzie, Ian R" sort="Mackenzie, Ian R" uniqKey="Mackenzie I" first="Ian R." last="Mackenzie">Ian R. Mackenzie</name><name sortKey="O Eill, Megan A" sort="O Eill, Megan A" uniqKey="O Eill M" first="Megan A." last="O Eill">Megan A. O Eill</name><name sortKey="Plotkin, Steven S" sort="Plotkin, Steven S" uniqKey="Plotkin S" first="Steven S." last="Plotkin">Steven S. Plotkin</name><name sortKey="Pokrishevsky, Edward" sort="Pokrishevsky, Edward" uniqKey="Pokrishevsky E" first="Edward" last="Pokrishevsky">Edward Pokrishevsky</name><name sortKey="Silverman, Judith M" sort="Silverman, Judith M" uniqKey="Silverman J" first="Judith M." last="Silverman">Judith M. Silverman</name><name sortKey="Yanai, Anat" sort="Yanai, Anat" uniqKey="Yanai A" first="Anat" last="Yanai">Anat Yanai</name><name sortKey="Yousefi, Masoud" sort="Yousefi, Masoud" uniqKey="Yousefi M" first="Masoud" last="Yousefi">Masoud Yousefi</name></country><country name="Australie"><noRegion><name sortKey="Yerbury, Justin J" sort="Yerbury, Justin J" uniqKey="Yerbury J" first="Justin J." last="Yerbury">Justin J. Yerbury</name></noRegion><name sortKey="Coleman, Bradley M" sort="Coleman, Bradley M" uniqKey="Coleman B" first="Bradley M." last="Coleman">Bradley M. Coleman</name><name sortKey="Corcoran, Lisa" sort="Corcoran, Lisa" uniqKey="Corcoran L" first="Lisa" last="Corcoran">Lisa Corcoran</name><name sortKey="Hill, Andrew F" sort="Hill, Andrew F" uniqKey="Hill A" first="Andrew F." last="Hill">Andrew F. Hill</name><name sortKey="Zeineddine, Rafaa" sort="Zeineddine, Rafaa" uniqKey="Zeineddine R" first="Rafaa" last="Zeineddine">Rafaa Zeineddine</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Kumita, Janet R" sort="Kumita, Janet R" uniqKey="Kumita J" first="Janet R." last="Kumita">Janet R. Kumita</name></noRegion><name sortKey="Luheshi, Leila M" sort="Luheshi, Leila M" uniqKey="Luheshi L" first="Leila M." last="Luheshi">Leila M. Luheshi</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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