The ability of differing subunit combinations of 5-HT3 receptors to form functional cell surface receptors was analyzed by a variety of approaches. The results revealed that 5-HT3 receptor assembly occurred within the endoplasmic reticulum (ER) and involved the interaction with chaperone proteins. The 5-HT3A subunit could assemble into functional homomeric receptors that were expressed on the cell surface. In contrast, the 5-HT3B subunit did not exhibit 5-hydroxytryptamine binding or function, could not assemble, and was efficiently retained and degraded within the ER. However, upon the coexpression of the 5-HT3A subunit, 5-HT3B could be “rescued” from the ER and transported to the cell surface to form functional heteromeric receptors with distinct functional characteristics. In support of the existence of homomeric 5-HT3 receptors in vivo, recombinantly expressed 5-HT3A receptors were capable of clustered cell surface expression in cortical neurons.
Boyd, G. W., Low, P., Dunlop, J. I., Robertson, L. A., Vardy, A., Lambert, J. J., Peters, J. A., & Connolly, C. N. (2002). Assembly and cell surface expression of homomeric and heteromeric 5-HT3 receptors: the role of oligomerization and chaperone proteins. Molecular and Cellular Neuroscience, 21(1), 38-50. https://doi.org/10.1006/mcne.2002.1160