Differential subcellular localization of RIC-3 Isoforms and their role in determining 5-HT3 receptor composition

Aixin Cheng, Karen A. Bollan, Sam M. Greenwood, Andrew J. Irving, Christopher N. Connolly

    Research output: Contribution to journalArticle

    27 Citations (Scopus)

    Abstract

    RIC-3 has been identified as a chaperone molecule involved in promoting the functional expression of nicotinic acetylcholine and 5-HT3 receptors in mammalian cells. In this study, we examined the effects of RIC-3a ( isoform a) and a truncated isoform ( isoform d) on RIC-3 localization, mobility, and aggregation and its effect on 5-HT3 receptor composition in mammalian cells. Human RIC-3a possesses an amino-terminal signal sequence that targets it to the endoplasmic reticulum where it is distributed within the reticular network, often forming large diffuse "slicks" and bright "halo" structures. RIC-3a is highly mobile within and between these compartments. Despite the propensity for RIC-3a to aggregate, its expression enhances the level of surface 5-HT3A (homomeric) receptors. In contrast, RIC-3a exerts an inhibitory action on the surface expression of heteromeric 5-HT3A/B receptors. RIC-3d exhibits an altered subcellular distribution, being localized to the endoplasmic reticulum, large diffuse slicks, tubulo-vesicular structures, and the Golgi. Bidirectional trafficking between the endoplasmic reticulum and Golgi suggests that RIC-3d constitutively cycles between these two compartments. In support of the large coiled-coil domain of RIC-3a being responsible for protein aggregation, RIC-3d, lacking this cytoplasmic domain, does not aggregate or induce the formation of bright aggregates. Regardless of these differences, isoform d is still capable of enhancing homomeric, and inhibiting heteromeric, 5-HT3 receptor expression. Thus, both isoforms of RIC-3 play a role in determining 5-HT3 receptor composition.

    Original languageEnglish
    Pages (from-to)26158-26166
    Number of pages9
    JournalJournal of Biological Chemistry
    Volume282
    Issue number36
    DOIs
    Publication statusPublished - 7 Sep 2007

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    Receptors, Serotonin, 5-HT3
    Protein Isoforms
    Endoplasmic Reticulum
    Chemical analysis
    Agglomeration
    Cells
    Protein Sorting Signals
    Acetylcholine
    Molecules
    Proteins

    Cite this

    Cheng, Aixin ; Bollan, Karen A. ; Greenwood, Sam M. ; Irving, Andrew J. ; Connolly, Christopher N. / Differential subcellular localization of RIC-3 Isoforms and their role in determining 5-HT3 receptor composition. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 36. pp. 26158-26166.
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    abstract = "RIC-3 has been identified as a chaperone molecule involved in promoting the functional expression of nicotinic acetylcholine and 5-HT3 receptors in mammalian cells. In this study, we examined the effects of RIC-3a ( isoform a) and a truncated isoform ( isoform d) on RIC-3 localization, mobility, and aggregation and its effect on 5-HT3 receptor composition in mammalian cells. Human RIC-3a possesses an amino-terminal signal sequence that targets it to the endoplasmic reticulum where it is distributed within the reticular network, often forming large diffuse {"}slicks{"} and bright {"}halo{"} structures. RIC-3a is highly mobile within and between these compartments. Despite the propensity for RIC-3a to aggregate, its expression enhances the level of surface 5-HT3A (homomeric) receptors. In contrast, RIC-3a exerts an inhibitory action on the surface expression of heteromeric 5-HT3A/B receptors. RIC-3d exhibits an altered subcellular distribution, being localized to the endoplasmic reticulum, large diffuse slicks, tubulo-vesicular structures, and the Golgi. Bidirectional trafficking between the endoplasmic reticulum and Golgi suggests that RIC-3d constitutively cycles between these two compartments. In support of the large coiled-coil domain of RIC-3a being responsible for protein aggregation, RIC-3d, lacking this cytoplasmic domain, does not aggregate or induce the formation of bright aggregates. Regardless of these differences, isoform d is still capable of enhancing homomeric, and inhibiting heteromeric, 5-HT3 receptor expression. Thus, both isoforms of RIC-3 play a role in determining 5-HT3 receptor composition.",
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    Differential subcellular localization of RIC-3 Isoforms and their role in determining 5-HT3 receptor composition. / Cheng, Aixin; Bollan, Karen A.; Greenwood, Sam M.; Irving, Andrew J.; Connolly, Christopher N.

    In: Journal of Biological Chemistry, Vol. 282, No. 36, 07.09.2007, p. 26158-26166.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Differential subcellular localization of RIC-3 Isoforms and their role in determining 5-HT3 receptor composition

    AU - Cheng, Aixin

    AU - Bollan, Karen A.

    AU - Greenwood, Sam M.

    AU - Irving, Andrew J.

    AU - Connolly, Christopher N.

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    N2 - RIC-3 has been identified as a chaperone molecule involved in promoting the functional expression of nicotinic acetylcholine and 5-HT3 receptors in mammalian cells. In this study, we examined the effects of RIC-3a ( isoform a) and a truncated isoform ( isoform d) on RIC-3 localization, mobility, and aggregation and its effect on 5-HT3 receptor composition in mammalian cells. Human RIC-3a possesses an amino-terminal signal sequence that targets it to the endoplasmic reticulum where it is distributed within the reticular network, often forming large diffuse "slicks" and bright "halo" structures. RIC-3a is highly mobile within and between these compartments. Despite the propensity for RIC-3a to aggregate, its expression enhances the level of surface 5-HT3A (homomeric) receptors. In contrast, RIC-3a exerts an inhibitory action on the surface expression of heteromeric 5-HT3A/B receptors. RIC-3d exhibits an altered subcellular distribution, being localized to the endoplasmic reticulum, large diffuse slicks, tubulo-vesicular structures, and the Golgi. Bidirectional trafficking between the endoplasmic reticulum and Golgi suggests that RIC-3d constitutively cycles between these two compartments. In support of the large coiled-coil domain of RIC-3a being responsible for protein aggregation, RIC-3d, lacking this cytoplasmic domain, does not aggregate or induce the formation of bright aggregates. Regardless of these differences, isoform d is still capable of enhancing homomeric, and inhibiting heteromeric, 5-HT3 receptor expression. Thus, both isoforms of RIC-3 play a role in determining 5-HT3 receptor composition.

    AB - RIC-3 has been identified as a chaperone molecule involved in promoting the functional expression of nicotinic acetylcholine and 5-HT3 receptors in mammalian cells. In this study, we examined the effects of RIC-3a ( isoform a) and a truncated isoform ( isoform d) on RIC-3 localization, mobility, and aggregation and its effect on 5-HT3 receptor composition in mammalian cells. Human RIC-3a possesses an amino-terminal signal sequence that targets it to the endoplasmic reticulum where it is distributed within the reticular network, often forming large diffuse "slicks" and bright "halo" structures. RIC-3a is highly mobile within and between these compartments. Despite the propensity for RIC-3a to aggregate, its expression enhances the level of surface 5-HT3A (homomeric) receptors. In contrast, RIC-3a exerts an inhibitory action on the surface expression of heteromeric 5-HT3A/B receptors. RIC-3d exhibits an altered subcellular distribution, being localized to the endoplasmic reticulum, large diffuse slicks, tubulo-vesicular structures, and the Golgi. Bidirectional trafficking between the endoplasmic reticulum and Golgi suggests that RIC-3d constitutively cycles between these two compartments. In support of the large coiled-coil domain of RIC-3a being responsible for protein aggregation, RIC-3d, lacking this cytoplasmic domain, does not aggregate or induce the formation of bright aggregates. Regardless of these differences, isoform d is still capable of enhancing homomeric, and inhibiting heteromeric, 5-HT3 receptor expression. Thus, both isoforms of RIC-3 play a role in determining 5-HT3 receptor composition.

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    M3 - Article

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    JF - Journal of Biological Chemistry

    SN - 0021-9258

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    ER -