AP-4 Mediates Export of ATG9A from the Trans-Golgi Network to Promote
AP-4 mediates export of ATG9A from the trans-Golgi PNAS PLUS network to promote autophagosome formation Rafael Matteraa,1, Sang Yoon Parka,1, Raffaella De Pacea, Carlos M. Guardiaa, and Juan S. Bonifacinoa,2 aCell Biology and Neurobiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 Edited by Pietro De Camilli, Howard Hughes Medical Institute and Yale University, New Haven, CT, and approved November 6, 2017 (received for review October 2, 2017) AP-4 is a member of the heterotetrameric adaptor protein (AP) mediated by a noncanonical YRYRF sequence in the receptor- complex family involved in protein sorting in the endomembrane associated, transmembrane AMPA receptor regulatory proteins system of eukaryotic cells. Interest in AP-4 has recently risen with (TARPs) (17). Finally, in the δ2 glutamate receptor protein, the discovery that mutations in any of its four subunits cause a binding to μ4 depends on several phenylalanine residues in a form of hereditary spastic paraplegia (HSP) with intellectual noncanonical context (18). disability. The critical sorting events mediated by AP-4 and the Interest in AP-4 has recently risen because of the discovery of pathogenesis of AP-4 deficiency, however, remain poorly under- mutations in genes encoding each of the subunits of AP-4 in stood. Here we report the identification of ATG9A, the only a subset of autosomal recessive hereditary spastic paraplegias multispanning membrane component of the core autophagy ma- (HSPs), namely, SPG47 (AP4B1/β4), SPG50 (AP4M1/μ4), SPG51 chinery, as a specific AP-4 cargo. AP-4 promotes signal-mediated (AP4E1/e), and SPG52 (AP4S1/σ4) (19–21).
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