title: Role of the RIC-3 protein in trafficking of serotonin and nicotinic acetylcholine receptors.
abstract: Neurotransmitter-gated receptors are assembled in the endoplasmic reticulum and transported to the cell surface through a process that might be of central importance to regulate the efficacy of synaptic transmission (Kneussel and Betz, 2000; Kittler and Moss, 2003). This process is relatively inefficient- what may be the consequence of tight quality controls that guarantee the functional competence of the final product. For this purpose, specific proteins involved in assembly and trafficking of receptors might be required (Keller and Taylor, 1999; Millar, 2003; Wanamaker et al., 2003). The RIC-3 protein could be one of them, as mutations in the ric-3 gene affect maturation of nicotinic acetylcholine receptors (nAChRs) in Caenorhabditis elegans (Halevi et al., 2002). Moreover, the human homolog hRIC-3 showed differential effects when coexpressed with several ligand-gated receptors (Halevi et al., 2003). Thus, it enhanced alpha7 nAChR expression while inhibiting expression of other nAChR subtypes (alpha4beta2 and alpha3beta4) and 5-HT3 serotonin receptors (5-HT3Rs). These opposite effects suggested that the RIC-3 protein might play a key role in the biogenesis of some ligand-gated receptors and prompted us to investigate how it performs its action. Here, we show that the RIC-3 protein acts as a barrier for some receptors like alpha4beta2 nAChRs and 5-HT3Rs, stopping the traffic of mature receptors to the membrane. In contrast, the inefficient transport of alpha7 nAChRs is enhanced by RIC-3 in a process in which certain amino acids at the amphipathic helix located at the C-terminal region of the large cytoplasmic domain are involved.
authors.affiliation: Instituto de Neurociencias de Alicante, UMH-CSIC, 03550 Sant Joan d'Alacant, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Castillo
authors.forename: José
authors.initials: J
authors.lastname: Mulet
authors.forename: Luis M
authors.initials: LM
authors.lastname: Gutiérrez
authors.forename: José A
authors.initials: JA
authors.lastname: Ortiz
authors.forename: Francisco
authors.initials: F
authors.lastname: Castelán
authors.forename: Susana
authors.initials: S
authors.lastname: Gerber
authors.forename: Salvador
authors.initials: S
authors.lastname: Sala
authors.forename: Francisco
authors.initials: F
authors.lastname: Sala
authors.forename: Manuel
authors.initials: M
authors.lastname: Criado
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000096:biosynthesis / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C496701:RIC3 protein, human; D011978:Receptors, Nicotinic; D011985:Receptors, Serotonin; D011994:Recombinant Proteins