Accumulation of AMPA receptors in autophagosomes in neuronal axons lacking adaptor protein AP-4.
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.
Matsuda
Shinji
S
Department of Physiology, School of Medicine, Keio University, Tokyo 160-8582, Japan.
Miura
Eriko
E
Matsuda
Keiko
K
Kakegawa
Wataru
W
Kohda
Kazuhisa
K
Watanabe
Masahiko
M
Yuzaki
Michisuke
M
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
D033964:Adaptor Protein Complex 4; D018091:Receptors, AMPA