Identification of brain substrates of transglutaminase by functional proteomics supports its role in neurodegenerative diseases.
Identifieur interne : 000031 ( Main/Exploration ); précédent : 000030; suivant : 000032Identification of brain substrates of transglutaminase by functional proteomics supports its role in neurodegenerative diseases.
Auteurs : William André [France] ; Isabelle Nondier [France] ; Maud Valensi [France] ; François Guillonneau [France] ; Christian Federici [France] ; Guylaine Hoffner [France] ; Philippe Djian [France]Source :
- Neurobiology of disease [ 1095-953X ] ; 2017.
Abstract
Transglutaminases are calcium-dependent enzymes that catalyze the formation of ε-(γ-glutamyl)lysine isopeptide bonds between specific glutamine and lysine residues. Some transglutaminase isoforms are present in the brain and are thought to participate in the protein aggregation characteristic of neurological diseases such as Huntington, Alzheimer's and Parkinson's disease. We have developed a functional proteomics strategy in which biotinylated amine-donor and amine-acceptor probes were used to identify the transglutaminase substrates present in brain. Bioinformatics analyses revealed that most of the 166 brain substrates identified interacted with huntingtin, the amyloid precursor protein or α-synuclein and that neurological disease was the most significant canonical pathway associated with the substrates. The physiological relevance of the substrates identified by mass spectrometry was confirmed by the fact that three of them (actin, β-tubulin and a neurofilament subunit) were polymerized in neuronal cells when cytosolic calcium concentration was raised. We also showed by in-situ immunolabeling that some of the substrates were part of the protein aggregates found in neurological diseases. These results strongly support the idea that the crosslinking activity of brain transglutaminase participates in the formation of the protein aggregates found in diseases of the central nervous system.
DOI: 10.1016/j.nbd.2017.01.007
PubMed: 28132929
Affiliations:
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3P5 Plateforme de protéomique, Université Paris Descartes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Cochin, INSERM U1016/CNRS UMR8104, Paris, France; 3P5 Plateforme de protéomique, Université Paris Descartes</wicri:regionArea><wicri:noRegion>Université Paris Descartes</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="region" nuts="2">Île-de-France</region></placeName><orgName type="university">Université Paris-Descartes</orgName><orgName type="institution" wicri:auto="newGroup">Sorbonne Paris Cité</orgName></affiliation></author><author><name sortKey="Federici, Christian" sort="Federici, Christian" uniqKey="Federici C" first="Christian" last="Federici">Christian Federici</name><affiliation wicri:level="4"><nlm:affiliation>Institut Cochin, INSERM U1016/CNRS UMR8104, Paris, France; 3P5 Plateforme de protéomique, Université Paris Descartes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Cochin, INSERM U1016/CNRS UMR8104, Paris, France; 3P5 Plateforme de protéomique, Université Paris Descartes</wicri:regionArea><wicri:noRegion>Université Paris Descartes</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="region" nuts="2">Île-de-France</region></placeName><orgName type="university">Université Paris-Descartes</orgName><orgName type="institution" wicri:auto="newGroup">Sorbonne Paris Cité</orgName></affiliation></author><author><name sortKey="Hoffner, Guylaine" sort="Hoffner, Guylaine" uniqKey="Hoffner G" first="Guylaine" last="Hoffner">Guylaine Hoffner</name><affiliation wicri:level="4"><nlm:affiliation>Laboratoire de physiologie cérébrale, UMR 8118, Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes, Paris, France. Electronic address: guylaine.hoffner@parisdescartes.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de physiologie cérébrale, UMR 8118, Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author><author><name sortKey="Djian, Philippe" sort="Djian, Philippe" uniqKey="Djian P" first="Philippe" last="Djian">Philippe Djian</name><affiliation wicri:level="4"><nlm:affiliation>Laboratoire de physiologie cérébrale, UMR 8118, Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes, Paris, France. Electronic address: philippe.djian@parisdescartes.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de physiologie cérébrale, UMR 8118, Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author></analytic><series><title level="j">Neurobiology of disease</title><idno type="eISSN">1095-953X</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Transglutaminases are calcium-dependent enzymes that catalyze the formation of ε-(γ-glutamyl)lysine isopeptide bonds between specific glutamine and lysine residues. Some transglutaminase isoforms are present in the brain and are thought to participate in the protein aggregation characteristic of neurological diseases such as Huntington, Alzheimer's and Parkinson's disease. We have developed a functional proteomics strategy in which biotinylated amine-donor and amine-acceptor probes were used to identify the transglutaminase substrates present in brain. Bioinformatics analyses revealed that most of the 166 brain substrates identified interacted with huntingtin, the amyloid precursor protein or α-synuclein and that neurological disease was the most significant canonical pathway associated with the substrates. The physiological relevance of the substrates identified by mass spectrometry was confirmed by the fact that three of them (actin, β-tubulin and a neurofilament subunit) were polymerized in neuronal cells when cytosolic calcium concentration was raised. We also showed by in-situ immunolabeling that some of the substrates were part of the protein aggregates found in neurological diseases. These results strongly support the idea that the crosslinking activity of brain transglutaminase participates in the formation of the protein aggregates found in diseases of the central nervous system.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Île-de-France</li></region><settlement><li>Paris</li></settlement><orgName><li>Sorbonne Paris Cité</li><li>Université Paris-Descartes</li></orgName></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Andre, William" sort="Andre, William" uniqKey="Andre W" first="William" last="André">William André</name></region><name sortKey="Djian, Philippe" sort="Djian, Philippe" uniqKey="Djian P" first="Philippe" last="Djian">Philippe Djian</name><name sortKey="Federici, Christian" sort="Federici, Christian" uniqKey="Federici C" first="Christian" last="Federici">Christian Federici</name><name sortKey="Guillonneau, Francois" sort="Guillonneau, Francois" uniqKey="Guillonneau F" first="François" last="Guillonneau">François Guillonneau</name><name sortKey="Hoffner, Guylaine" sort="Hoffner, Guylaine" uniqKey="Hoffner G" first="Guylaine" last="Hoffner">Guylaine Hoffner</name><name sortKey="Nondier, Isabelle" sort="Nondier, Isabelle" uniqKey="Nondier I" first="Isabelle" last="Nondier">Isabelle Nondier</name><name sortKey="Valensi, Maud" sort="Valensi, Maud" uniqKey="Valensi M" first="Maud" last="Valensi">Maud Valensi</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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