Dual role of the RIC-3 protein in trafficking of serotonin and nicotinic acetylcholine receptors

J Biol Chem. 2005 Jul 22;280(29):27062-8. doi: 10.1074/jbc.M503746200. Epub 2005 May 31.

Abstract

The ric-3 gene is required for maturation of nicotinic acetylcholine receptors in Caenorhabditis elegans. The human homolog of RIC-3, hRIC-3, enhances expression of alpha7 nicotinic receptors in Xenopus laevis oocytes, whereas it totally abolishes expression of alpha4beta2 nicotinic and 5-HT3 serotonergic receptors. Both the N-terminal region of hRIC-3, which contains two transmembrane segments, and the C-terminal region are needed for these differential effects. hRIC-3 inhibits receptor expression by hindering export of mature receptors to the cell membrane. By using chimeric proteins made of alpha7 and 5-HT3 receptors, we have shown that the presence of an extracellular isoleucine close to the first transmembrane receptor fragment is responsible for the transport arrest induced by hRIC-3. Enhancement of alpha7 receptor expression occurs, at least, at two levels: by increasing the number of mature receptors and facilitating its transport to the membrane. Certain amino acids of a putative amphipathic helix present at the large cytoplasmic region of the alpha7 subunit are required for these actions. Therefore, hRIC-3 can act as a specific regulator of receptor expression at different levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins
  • Cell Line
  • Cell Membrane / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Protein Transport
  • Proteins / physiology*
  • Receptors, Nicotinic / metabolism*
  • Receptors, Serotonin, 5-HT3 / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Serotonin / metabolism*
  • Transfection
  • alpha7 Nicotinic Acetylcholine Receptor

Substances

  • Carrier Proteins
  • Chrna7 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • RIC3 protein, human
  • Receptors, Nicotinic
  • Receptors, Serotonin, 5-HT3
  • Recombinant Fusion Proteins
  • alpha7 Nicotinic Acetylcholine Receptor
  • Serotonin