Receptors look outward: revealing signals that bring excitation to synapses.

Defining the molecular mechanisms that govern the trafficking of glutamate receptors to excitatory synaptic contacts is fundamental to understanding the mechanisms that regulate synapse maturation and neuronal excitability. Previous studies have identified several scaffolding molecules and adaptor proteins that regulate glutamate receptor trafficking and retention at the synapse. Recent work, however, has elucidated new players such as the N-cadherin adhesion complex, and members of the pentraxin family that regulate clustering of glutamate receptors through extracellular protein interactions. Here, we highlight recently identified modes that regulate glutamate receptor clustering, and discuss their relevance to synapse maturation.