Assembly and cell surface expression of homomeric and heteromeric 5-HT3 receptors: the role of oligomerization and chaperone proteins.
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.
D000818:Animals; D000831:Animals, Newborn; D019556:COS Cells; D037281:Calnexin / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D006031:Glycosylation; D006360:Heat-Shock Proteins; D007150:Immunohistochemistry; D018832:Molecular Chaperones / Q000378:metabolism*; D009420:Nervous System / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009865:Oocytes; D011108:Polymers / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D011869:Radioligand Assay; D051381:Rats; D011985:Receptors, Serotonin / Q000096:biosynthesis* / Q000235:genetics; D044406:Receptors, Serotonin, 5-HT3; D014982:Xenopus laevis
D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D011108:Polymers; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D037281:Calnexin