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Accumulation of AMPA Receptors in Autophagosomes in Neuronal Axons Lacking Adaptor Protein AP-4

2008; Cell Press; Volume: 57; Issue: 5 Linguagem: Inglês

10.1016/j.neuron.2008.02.012

1097-4199

Shinji Matsuda, Eriko Miura, Keiko Matsuda, Wataru Kakegawa, Kazuhisa Kohda, Masahiko Watanabe, Michisuke Yuzaki,

Endoplasmic Reticulum Stress and Disease

AP-4 is a member of the adaptor protein complexes, which control vesicular trafficking of membrane proteins. Although AP-4 has been suggested to contribute to basolateral sorting in epithelial cells, its function in neurons is unknown. Here, we show that disruption of the gene encoding the β subunit of AP-4 resulted in increased accumulation of axonal autophagosomes, which contained AMPA receptors and transmembrane AMPA receptor regulatory proteins (TARPs), in axons of hippocampal neurons and cerebellar Purkinje cells both in vitro and in vivo. AP-4 indirectly associated with the AMPA receptor via TARPs, and the specific disruption of the interaction between AP-4 and TARPs caused the mislocalization of endogenous AMPA receptors in axons of wild-type neurons. These results indicate that AP-4 may regulate proper somatodendritic-specific distribution of its cargo proteins, including AMPA receptor-TARP complexes and the autophagic pathway in neurons.