Pruning and loss of excitatory synapses by the parkin ubiquitin ligase.

Mutations in the PARK2 gene cause hereditary Parkinson disease (PD). The PARK2 gene product, termed parkin, is an E3 ubiquitin ligase that mediates the transfer of ubiquitin onto diverse substrate proteins. Despite progress in defining the molecular properties and substrates of parkin, little is known about its physiological function.

Endocytosis and degradative sorting of NMDA receptors by conserved membrane-proximal signals.

Regulation of the abundance of NMDA receptors (NMDARs) at excitatory synapses is critical during changes in synaptic efficacy underlying learning and memory as well as during synapse formation throughout neural development. However, the molecular signals that govern NMDAR delivery, maintenance, and internalization remain unclear. In this study, we identify a conserved family of membrane-proximal endocytic signals, two within the NMDAR type 1 (NR1) subunit and one within the NR2A and NR2B subunits, necessary and sufficient to drive the internalization of NMDARs.

Activity-dependent mRNA splicing controls ER export and synaptic delivery of NMDA receptors.

Activity-dependent targeting of NMDA receptors (NMDARs) is a key feature of synapse formation and plasticity. Although mechanisms for rapid trafficking of glutamate receptors have been identified, the molecular events underlying chronic accumulation or loss of synaptic NMDARs have remained unclear. Here we demonstrate that activity controls NMDAR synaptic accumulation by regulating forward trafficking at the endoplasmic reticulum (ER).