title: Accumulation of AMPA receptors in autophagosomes in neuronal axons lacking adaptor protein AP-4.
abstract: 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 beta 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.
authors.affiliation: Department of Physiology, School of Medicine, Keio University, Tokyo 160-8582, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsuda
authors.forename: Eriko
authors.initials: E
authors.lastname: Miura
authors.forename: Keiko
authors.initials: K
authors.lastname: Matsuda
authors.forename: Wataru
authors.initials: W
authors.lastname: Kakegawa
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Kohda
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Michisuke
authors.initials: M
authors.lastname: Yuzaki
mesh_terms: D033964:Adaptor Protein Complex 4 / Q000172:deficiency* / Q000235:genetics; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D001369:Axons / Q000737:chemistry / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009474:Neurons / Q000737:chemistry / Q000502:physiology; D010588:Phagosomes / Q000737:chemistry / Q000502:physiology*; D011817:Rabbits; D018091:Receptors, AMPA / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D033964:Adaptor Protein Complex 4; D018091:Receptors, AMPA