Multiple Trafficking Signals Regulate Kainate Receptor KA2 Subunit Surface Expression

摘要: The kainate receptor subunit KA2 does not form functional homomeric channels despite its structural similarity to the glutamate 5-7subunits and high agonist binding affinity in vitro assays. In this study, we first demonstrate that receptors fail reach plasma membrane then identify molecular mechanisms preventing surface expression. Specifically, show subunits homooligomeric are confined endoplasmic reticulum (ER). We that, both heterologous expression systems primary neurons, intracellular retention of is caused by misfolding but, rather, mediated through discrete protein trafficking signals, including an arginine-rich ER retention/retrieval motif a di-leucine endocytic sequence C terminus subunit. Disruption these motifs results exit remain nonfunctional. Furthermore, our data suggest signal sterically shielded during heteromeric assembly, allowing delivery membrane. Taken together, illustrate novel regulatory control receptors.