The promiscuous role of the epsilon subunit in GABA(A) receptor biogenesis

Karen A. Bollan, Roland Baur, Tim G. Hales, Erwin Sigel, Christopher N. Connolly

    Research output: Contribution to journalArticle

    27 Citations (Scopus)

    Abstract

    The formation of alpha 1 beta 2 gamma 2 epsilon receptors suggests that the e subunit does not displace the single gamma 2 subunit in alpha 1 beta 2 gamma 2 receptors. Thus, e must replace cc and/or beta subunit(s) if the pentameric receptor structure is to be preserved. To assess the potential for which subunit is replaced in alpha beta epsilon and alpha beta gamma epsilon receptors we analyzed the assembly and functional expression of the e subunit with respect to alpha 1, beta 2 and gamma 2 subunits. Using concatenated subunits, we have determined that e is capable of substituting for either (but not both) of the alpha subunits, one of the 0 subunits, and possibly the gamma 2 subunit. However, the most likely sites at which the e subunit may contribute to receptor function appears to be at position I (replaces alpha 1) in alpha beta gamma epsilon (epsilon-beta 2-alpha 1-beta 2-gamma 2) receptors, or at position 4 (replaces beta 2) in alpha beta epsilon (alpha 1-beta 2-alpha 1-epsilon-beta 2) receptors. In both cases, it appears that only a single GABA binding site is present. (c) 2007 Elsevier Inc. All rights reserved.

    Original languageEnglish
    Pages (from-to)610-621
    Number of pages12
    JournalMolecular and Cellular Neuroscience
    Volume37
    Issue number3
    DOIs
    Publication statusPublished - Mar 2008

    Keywords

    • GABA(A) receptor
    • assembly
    • biogenesis
    • stoichiometry
    • epsilon
    • endoplasmic reticulum
    • cell surface
    • spontaneous
    • CELL-SURFACE EXPRESSION
    • GATED ION CHANNELS
    • BETA-SUBUNITS
    • A RECEPTORS
    • INTERSUBUNIT CONTACTS
    • EPILEPSY MUTATION
    • ASSEMBLY SIGNALS
    • FEBRILE SEIZURES
    • XENOPUS-OOCYTES
    • THETA SUBUNITS

    Cite this

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    title = "The promiscuous role of the epsilon subunit in GABA(A) receptor biogenesis",
    abstract = "The formation of alpha 1 beta 2 gamma 2 epsilon receptors suggests that the e subunit does not displace the single gamma 2 subunit in alpha 1 beta 2 gamma 2 receptors. Thus, e must replace cc and/or beta subunit(s) if the pentameric receptor structure is to be preserved. To assess the potential for which subunit is replaced in alpha beta epsilon and alpha beta gamma epsilon receptors we analyzed the assembly and functional expression of the e subunit with respect to alpha 1, beta 2 and gamma 2 subunits. Using concatenated subunits, we have determined that e is capable of substituting for either (but not both) of the alpha subunits, one of the 0 subunits, and possibly the gamma 2 subunit. However, the most likely sites at which the e subunit may contribute to receptor function appears to be at position I (replaces alpha 1) in alpha beta gamma epsilon (epsilon-beta 2-alpha 1-beta 2-gamma 2) receptors, or at position 4 (replaces beta 2) in alpha beta epsilon (alpha 1-beta 2-alpha 1-epsilon-beta 2) receptors. In both cases, it appears that only a single GABA binding site is present. (c) 2007 Elsevier Inc. All rights reserved.",
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    author = "Bollan, {Karen A.} and Roland Baur and Hales, {Tim G.} and Erwin Sigel and Connolly, {Christopher N.}",
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    language = "English",
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    The promiscuous role of the epsilon subunit in GABA(A) receptor biogenesis. / Bollan, Karen A.; Baur, Roland; Hales, Tim G.; Sigel, Erwin; Connolly, Christopher N.

    In: Molecular and Cellular Neuroscience, Vol. 37, No. 3, 03.2008, p. 610-621.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - The promiscuous role of the epsilon subunit in GABA(A) receptor biogenesis

    AU - Bollan, Karen A.

    AU - Baur, Roland

    AU - Hales, Tim G.

    AU - Sigel, Erwin

    AU - Connolly, Christopher N.

    PY - 2008/3

    Y1 - 2008/3

    N2 - The formation of alpha 1 beta 2 gamma 2 epsilon receptors suggests that the e subunit does not displace the single gamma 2 subunit in alpha 1 beta 2 gamma 2 receptors. Thus, e must replace cc and/or beta subunit(s) if the pentameric receptor structure is to be preserved. To assess the potential for which subunit is replaced in alpha beta epsilon and alpha beta gamma epsilon receptors we analyzed the assembly and functional expression of the e subunit with respect to alpha 1, beta 2 and gamma 2 subunits. Using concatenated subunits, we have determined that e is capable of substituting for either (but not both) of the alpha subunits, one of the 0 subunits, and possibly the gamma 2 subunit. However, the most likely sites at which the e subunit may contribute to receptor function appears to be at position I (replaces alpha 1) in alpha beta gamma epsilon (epsilon-beta 2-alpha 1-beta 2-gamma 2) receptors, or at position 4 (replaces beta 2) in alpha beta epsilon (alpha 1-beta 2-alpha 1-epsilon-beta 2) receptors. In both cases, it appears that only a single GABA binding site is present. (c) 2007 Elsevier Inc. All rights reserved.

    AB - The formation of alpha 1 beta 2 gamma 2 epsilon receptors suggests that the e subunit does not displace the single gamma 2 subunit in alpha 1 beta 2 gamma 2 receptors. Thus, e must replace cc and/or beta subunit(s) if the pentameric receptor structure is to be preserved. To assess the potential for which subunit is replaced in alpha beta epsilon and alpha beta gamma epsilon receptors we analyzed the assembly and functional expression of the e subunit with respect to alpha 1, beta 2 and gamma 2 subunits. Using concatenated subunits, we have determined that e is capable of substituting for either (but not both) of the alpha subunits, one of the 0 subunits, and possibly the gamma 2 subunit. However, the most likely sites at which the e subunit may contribute to receptor function appears to be at position I (replaces alpha 1) in alpha beta gamma epsilon (epsilon-beta 2-alpha 1-beta 2-gamma 2) receptors, or at position 4 (replaces beta 2) in alpha beta epsilon (alpha 1-beta 2-alpha 1-epsilon-beta 2) receptors. In both cases, it appears that only a single GABA binding site is present. (c) 2007 Elsevier Inc. All rights reserved.

    KW - GABA(A) receptor

    KW - assembly

    KW - biogenesis

    KW - stoichiometry

    KW - epsilon

    KW - endoplasmic reticulum

    KW - cell surface

    KW - spontaneous

    KW - CELL-SURFACE EXPRESSION

    KW - GATED ION CHANNELS

    KW - BETA-SUBUNITS

    KW - A RECEPTORS

    KW - INTERSUBUNIT CONTACTS

    KW - EPILEPSY MUTATION

    KW - ASSEMBLY SIGNALS

    KW - FEBRILE SEIZURES

    KW - XENOPUS-OOCYTES

    KW - THETA SUBUNITS

    U2 - 10.1016/j.mcn.2007.12.011

    DO - 10.1016/j.mcn.2007.12.011

    M3 - Article

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    EP - 621

    JO - Molecular and Cellular Neuroscience

    JF - Molecular and Cellular Neuroscience

    SN - 1044-7431

    IS - 3

    ER -