摘要：SummaryThe endoplasmic reticulum membrane complex (EMC) plays a critical role in the biogenesis of tail-anchored proteins and a subset of multi-pass membrane proteins in the endoplasmic reticulum (ER). However, because of nearly exclusive expression of neurotransmitter-gated ion channels in the central nervous system (CNS), the role of the EMC in their biogenesis is not well understood. In this study, we demonstrated that the EMC positively regulates the surface trafficking and thus function of endogenous γ-aminobutyric acid type A (GABAA) receptors, the primary inhibitory ion channels in the mammalian brain. Moreover, among ten EMC subunits, EMC3 and EMC6 have the most prominent effect, and overexpression of EMC3 or EMC6 is sufficient to restore the function of epilepsy-associated GABAAreceptor variants. In addition, EMC3 and EMC6 demonstrate endogenous interactions with major neuroreceptors, which depends on their transmembrane domains, suggesting a general role of the EMC in the biogenesis of neuroreceptors.Graphical abstractDisplay OmittedHighlights•EMC3 and EMC6 positively regulate the function of endogenous GABAAreceptors•The EMC interacts with major endogenous neuroreceptors•The EMC transmembrane domains contribute to the interaction with GABAAreceptors•Overexpressing the EMC restores the function of GABAAreceptor variantsBiological sciences; Molecular biology; Neuroscience; Molecular neuroscience; Cell biology
