Assembly and cell surface expression of homomeric and heteromeric 5-HT3 receptors: the role of oligomerization and chaperone proteins

Mol Cell Neurosci. 2002 Sep;21(1):38-50. doi: 10.1006/mcne.2002.1160.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • COS Cells
  • Calnexin / metabolism
  • Carrier Proteins / metabolism
  • Cell Membrane / metabolism*
  • Cells, Cultured
  • Cerebral Cortex / metabolism
  • Endoplasmic Reticulum / metabolism
  • Glycosylation
  • Heat-Shock Proteins*
  • Immunohistochemistry
  • Molecular Chaperones / metabolism*
  • Nervous System / metabolism*
  • Neurons / metabolism*
  • Oocytes
  • Polymers / metabolism
  • Protein Transport / physiology
  • Radioligand Assay
  • Rats
  • Receptors, Serotonin / biosynthesis*
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin, 5-HT3
  • Xenopus laevis

Substances

  • Carrier Proteins
  • Heat-Shock Proteins
  • Molecular Chaperones
  • Polymers
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • Calnexin
  • molecular chaperone GRP78