Polarized sorting of AMPA receptors to the somatodendritic domain is regulated by adaptor protein AP-4.

Neurons are highly polarized cells comprising somatodendritic and axonal domains. For proper neuronal function, such as neurotransmission and synaptic plasticity, membrane proteins must be transported to precise positions. alpha-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-type glutamate receptors (AMPA receptors) are membrane proteins localized in the somatodendritic domain. AMPA receptors mediate excitatory synaptic transmission; thus, regulation of the intracellular trafficking of AMPA receptors has a critical role in synaptic plasticity. An understanding of the molecular mechanisms that regulate AMPA receptor trafficking is essential for gaining further insight into neuronal function. Despite its importance, however, how neurons selectively transport AMPA receptors to the somatodendritic domain is largely unknown. In this Update Article, we discuss recent progress in studies of the mechanisms underlying the somatodendritic targeting of AMPA receptors in neurons.