Dual Role of the RIC-3 Protein in Trafficking of Serotonin and Nicotinic Acetylcholine Receptors

• Published in: The Journal of biological chemistry 2005-07, Vol.280 (29), p.27062-27068
• Main Authors: Castillo, Mar, Mulet, José, Gutiérrez, Luis M., Ortiz, José A., Castelán, Francisco, Gerber, Susana, Sala, Salvador, Sala, Francisco, Criado, Manuel
• Format: Article
• Language: English
• Subjects: alpha7 Nicotinic Acetylcholine Receptor; 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
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M503746200

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 α7 nicotinic receptors in Xenopus laevis oocytes, whereas it totally abolishes expression of α4β2 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 α7 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 α7 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 α7 subunit are required for these actions. Therefore, hRIC-3 can act as a specific regulator of receptor expression at different levels.