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EFA6A, an Exchange Factor for Arf6, Regulates NGF-Dependent TrkA Recycling From Early Endosomes and Neurite Outgrowth in PC12 Cells.
- Source :
-
Traffic (Copenhagen, Denmark) [Traffic] 2024 May; Vol. 25 (5), pp. e12936. - Publication Year :
- 2024
-
Abstract
- Endosomal trafficking of TrkA is a critical process for nerve growth factor (NGF)-dependent neuronal cell survival and differentiation. The small GTPase ADP-ribosylation factor 6 (Arf6) is implicated in NGF-dependent 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-specific guanine nucleotide exchange factor, was abundantly expressed in PC12 cells and that knockdown of EFA6A significantly inhibited NGF-dependent 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-terminal 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-dependent TrkA trafficking compared with wild-type neurons. These findings provide the first evidence for EFA6A as a key regulator of NGF-dependent TrkA trafficking and signaling.<br /> (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Subjects :
- Animals
Mice
Rats
Ganglia, Spinal metabolism
Mice, Knockout
PC12 Cells
Protein Transport
ADP-Ribosylation Factor 6
ADP-Ribosylation Factors metabolism
ADP-Ribosylation Factors genetics
Endosomes metabolism
Guanine Nucleotide Exchange Factors metabolism
Guanine Nucleotide Exchange Factors genetics
Nerve Growth Factor metabolism
Neuronal Outgrowth
Receptor, trkA metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1600-0854
- Volume :
- 25
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Traffic (Copenhagen, Denmark)
- Publication Type :
- Academic Journal
- Accession number :
- 38725127
- Full Text :
- https://doi.org/10.1111/tra.12936