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Publication : Accumulation of AMPA receptors in autophagosomes in neuronal axons lacking adaptor protein AP-4.

First Author  Matsuda S Year  2008
Journal  Neuron Volume  57
Issue  5 Pages  730-45
PubMed ID  18341993 Mgi Jnum  J:135974
Mgi Id  MGI:3794899 Doi  10.1016/j.neuron.2008.02.012
Citation  Matsuda S, et al. (2008) Accumulation of AMPA receptors in autophagosomes in neuronal axons lacking adaptor protein AP-4. Neuron 57(5):730-45
abstractText  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.
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