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NACHO Mediates Nicotinic Acetylcholine Receptor Function throughout the Brain.
Matta, Jose A; Gu, Shenyan; Davini, Weston B; Lord, Brian; Siuda, Edward R; Harrington, Anthony W; Bredt, David S.
Afiliación
  • Matta JA; Neuroscience Discovery, Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, USA.
  • Gu S; Neuroscience Discovery, Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, USA.
  • Davini WB; Neuroscience Discovery, Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, USA.
  • Lord B; Neuroscience Discovery, Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, USA.
  • Siuda ER; Neuroscience Discovery, Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, USA.
  • Harrington AW; Neuroscience Discovery, Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, USA.
  • Bredt DS; Neuroscience Discovery, Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, USA. Electronic address: dbredt@its.jnj.com.
Cell Rep ; 19(4): 688-696, 2017 04 25.
Article en En | MEDLINE | ID: mdl-28445721
Neuronal nicotinic acetylcholine receptors (nAChRs) participate in diverse aspects of brain function and mediate behavioral and addictive properties of nicotine. Neuronal nAChRs derive from combinations of α and ß subunits, whose assembly is tightly regulated. NACHO was recently identified as a chaperone for α7-type nAChRs. Here, we find NACHO mediates assembly of all major classes of presynaptic and postsynaptic nAChR tested. NACHO acts at early intracellular stages of nAChR subunit assembly and then synergizes with RIC-3 for receptor surface expression. NACHO knockout mice show profound deficits in binding sites for α-bungarotoxin, epibatidine, and conotoxin MII, illustrating essential roles for NACHO in proper assembly of α7-, α4ß2-, and α6-containing nAChRs, respectively. By contrast, GABAA receptors are unaffected consistent with NACHO specifically modulating nAChRs. NACHO knockout mice show abnormalities in locomotor and cognitive behaviors compatible with nAChR deficiency and underscore the importance of this chaperone for physiology and disease associated with nAChRs.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Encéfalo / Receptores Nicotínicos / Chaperonas Moleculares Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Encéfalo / Receptores Nicotínicos / Chaperonas Moleculares Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos