Molecular characterization and localization of the RIC-3 protein, an effector of nicotinic acetylcholine receptor expression.
The RIC-3 protein acts as a regulator of acetylcholine nicotinic receptor (nAChR) expression. In Xenopus laevis oocytes the human RIC-3 (hRIC-3) protein enhances expression of alpha7 receptors and abolishes expression of alpha4beta2 receptors. In vitro translation of hRIC-3 evidenced its membrane insertion but not the role as signal peptide of its first transmembrane domain (TMD). When the TMDs of hRIC-3 were substituted, its effects on nAChR expression were attenuated. A certain linker length between the TMDs was also needed for alpha7 expression enhancement but not for alpha4beta2 inhibition. A combination of increased alpha7 receptor steady state levels, facilitated transport and reduced receptor internalization appears to be responsible for the increase in alpha7 membrane expression induced by hRIC-3. Antibodies against hRIC-3 showed its expression in SH-SY5Y and PC12 cells and its induction upon differentiation. Immunohistochemistry demonstrated the presence of RIC-3 in rat brain localized, in general, in places where alpha7 nAChRs were found.
Castelán
Francisco
F
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d'Alacant, Alicante, Spain.
Castillo
Mar
M
Mulet
José
J
Sala
Salvador
S
Sala
Francisco
F
Domínguez Del Toro
Eduardo
E
Criado
Manuel
M
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D019556:COS Cells; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004705:Endocytosis / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D009420:Nervous System / Q000378:metabolism*; D009865:Oocytes; D016716:PC12 Cells; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D014982:Xenopus laevis; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; C496701:RIC3 protein, human; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2