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The small GTPase ADP\u2010ribosylation factor 6 (Arf6) is implicated in NGF\u2010dependent processes in PC12 cells through endosomal trafficking and actin cytoskeleton reorganization. However, the regulatory mechanism for Arf6 in NGF signaling is largely unknown. In this study, we demonstrated that EFA6A, an Arf6\u2010specific guanine nucleotide exchange factor, was abundantly expressed in PC12 cells and that knockdown of EFA6A significantly inhibited NGF\u2010dependent Arf6 activation, TrkA recycling from early endosomes to the cell surface, prolonged ERK1\/2 phosphorylation, and neurite outgrowth. We also demonstrated that EFA6A forms a protein complex with TrkA through its N\u2010terminal region, thereby enhancing its catalytic activity for Arf6. Similarly, we demonstrated that EFA6A forms a protein complex with TrkA in cultured dorsal root ganglion (DRG) neurons. Furthermore, cultured DRG neurons from EFA6A knockout mice exhibited disturbed NGF\u2010dependent TrkA trafficking compared with wild\u2010type neurons. These findings provide the first evidence for EFA6A as a key regulator of NGF\u2010dependent TrkA trafficking and signaling.<\/jats:p>","DOI":"10.1111\/tra.12936","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T00:25:34Z","timestamp":1715300734000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>EFA6A<\/scp>\n                    , an Exchange Factor for Arf6, Regulates\n                    <scp>NGF<\/scp>\n                    \u2010Dependent\n                    <scp>TrkA<\/scp>\n                    Recycling From Early Endosomes and Neurite Outgrowth in\n                    <scp>PC12<\/scp>\n                    Cells"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8241-3631","authenticated-orcid":false,"given":"Masahiro","family":"Fukaya","sequence":"first","affiliation":[{"name":"Department of Anatomy Kitasato University School of 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