Nedd4-mediated AMPA receptor ubiquitination regulates receptor turnover and trafficking.

摘要: J. Neurochem. (2011) 119, 27–39. Abstract α-Amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptors (AMPARs) are the primary mediators of excitatory synaptic transmission in brain. Alterations AMPAR localization and turnover have been considered critical mechanisms underpinning plasticity higher brain functions, but molecular processes that control trafficking stability still not fully understood. Here, we report mammalian AMPARs subject to ubiquitination neurons transfected heterologous cells. Ubiquitination facilitates endocytosis, leading a reduction cell-surface total receptor abundance. Mutation lysine residues arginine at glutamate subunit 1 (GluA1) C-terminus dramatically reduces GluA1 abolishes ubiquitin-dependent internalization degradation, indicating residues, particularly K868, sites ubiquitination. We also find E3 ligase neural precursor cell expressed, developmentally down-regulated 4 (Nedd4) is enriched synaptosomes co-localizes associates with neurons. Nedd4 expression leads ubiquitination, reduced surface suppressed transmission. Conversely, knockdown by specific siRNAs These data indicate ubiquitin responsible for modification regulates multiple aspects biology including trafficking, stability.