Intersubunit contacts governing assembly of the mammalian nicotinic acetylcholine receptor

Hans Jürgen Kreienkamp, Robert K. Maeda, Steven M Sine, Palmer Taylor

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Through specific intersubunit contacts, the four subunits of the nicotinic acetylcholine receptor assemble into an α2βγδ pentamer. The specificity of subunit association leads to formation of proper ligand binding sites and to transport of assembled pentamers to the cell surface. To identify determinants of subunit association, we constructed chimeric subunits, transfected them into HEK 293 cells, and studied their association with wild-type subunits. We used βγ chimeras to determine sequences that associate with the a subunit to form a ligand binding site and found residues 21-131 of the y subunit sufficient to form the site. Residues 51-131 of the β subunit do not form a binding site, but do promote surface expression of pentamers; of these residues, R117 is key for surface expression. We studied formation of tetramers by α and γ subunits and dimers by a and S subunits, and used γδ chimeras to identify sequences that result in either dimers or tetramers. The conserved residues 1145 and T150 of the γ subunit promote αγαγ tetramer formation, whereas the corresponding residues in the δ subunit, K145 and K150, allow only αδ dimer formation.

Original languageEnglish (US)
Pages (from-to)635-644
Number of pages10
JournalNeuron
Volume14
Issue number3
DOIs
StatePublished - 1995

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Nicotinic Receptors
Binding Sites
Ligands
HEK293 Cells

ASJC Scopus subject areas

  • Neuroscience(all)

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Intersubunit contacts governing assembly of the mammalian nicotinic acetylcholine receptor. / Kreienkamp, Hans Jürgen; Maeda, Robert K.; Sine, Steven M; Taylor, Palmer.

In: Neuron, Vol. 14, No. 3, 1995, p. 635-644.

Research output: Contribution to journalArticle

Kreienkamp, Hans Jürgen ; Maeda, Robert K. ; Sine, Steven M ; Taylor, Palmer. / Intersubunit contacts governing assembly of the mammalian nicotinic acetylcholine receptor. In: Neuron. 1995 ; Vol. 14, No. 3. pp. 635-644.
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