The RNA modification N 6 -methyladenosine (m 6 A) influences mRNA stability and cell-type-specific developmental programming, and is highly abundant in the adult brain. However, it has not been determined whether m 6 A is dynamically regulated by experience.

The delicate balance between endocytosis and recycling of the cell surface receptors (NMDAR and AMPAR) is essential for controlling their surface levels and degradation, and is regulated by numerous processes including lateral membrane diffusion, scaffolding protein interactions and posttranslational modifications. Generally the NMDARs undergo activity-dependent endocytosis within clathrin-coated vesicles. They then enter the endosomal system where they are either sorted into the degradative lysosomal pathway, or are replenished via endosomal recycling. Defects in endosomal trafficking therefore lead to perturbed homeostasis of NMDARs. Our recent findings provide a comprehensive understanding of how post-translational modifications of NMDAR define an extended electrostatic peptide code for cargo sorting and influence their interactions with the trafficking machinery. Currently, I am trying to understand the mechanistic basis of intracellular trafficking in NMDAR receptor homeostasis. In my talk, I will be discussing about some of our efforts in the basic studies of the structure and function of SNX27, a unique member of PX-FERM module, that control membrane trafficking. Additionally, I will highlight the novel role for phosphorylation of the NMDARs in promoting SNX27-retromer interactions, which may have significant implications for activity-dependent trafficking of NMDARs during synaptic potentiation.

SUMMARY AMPA receptors (AMPARs) have recently been shown to undergo post-translational ubiquitination in mammalian neurons. However, the underlying molecular mechanisms are poorly understood and remain controversial. Here, we report that all four AMPAR subunits (GluA1–4) are rapidly ubiquitinated upon brief application of AMPA or bicuculline in cultured neurons. This process is Ca2+ dependent and requires the activity of L-type voltage-gated Ca2+ channels and Ca2+/calmodulin-dependent kinase II. The ubiquitination of all subunits occurs exclusively on AMPARs located on the plasma membrane post-endocytosis. The sites of ubiquitination were mapped to Lys-868 in GluA1 and Lys-870/Lys-882 in GluA2 C-terminals. Mutation of these lysines did not affect basal surface expression or AMPA-induced internalization of GluA1 and GluA2 subunits. Instead, it reduced the intracellular trafficking of AMPARs to the late endosomes and thus protein degradation. These data indicate that ubiquitination is an important regulatory signal for controlling AMPAR function, which may be crucial for synaptic plasticity.