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Publication : EFA6A, a guanine nucleotide exchange factor for Arf6, interacts with sorting nexin-1 and regulates neurite outgrowth.

First Author  Fukaya M Year  2014
Journal  J Neurochem Volume  129
Issue  1 Pages  21-36
PubMed ID  24261326 Mgi Jnum  J:208189
Mgi Id  MGI:5562465 Doi  10.1111/jnc.12524
Citation  Fukaya M, et al. (2014) EFA6A, a guanine nucleotide exchange factor for Arf6, interacts with sorting nexin-1 and regulates neurite outgrowth. J Neurochem 129(1):21-36
abstractText  The membrane trafficking and actin cytoskeleton remodeling mediated by ADP ribosylation factor 6 (Arf6) are functionally linked to various neuronal processes including neurite formation and maintenance, neurotransmitter release, and receptor internalization. EFA6A is an Arf6-specific guanine nucleotide exchange factor that is abundantly expressed in the brain. In this study, we identified sorting nexin-1 (SNX1), a retromer component that is implicated in endosomal sorting and trafficking, as a novel interacting partner for EFA6A by yeast two-hybrid screening. The interaction was mediated by the C-terminal region of EFA6A and a BAR domain of SNX1, and further confirmed by pull-down assay and immunoprecipitation from mouse brain lysates. In situ hybridization analysis demonstrated the widespread expression of SNX1 in the mouse brain, which overlapped with the expression of EFA6A in the forebrain. Immunofluorescent analysis revealed the partial colocalization of EFA6A and SNX1 in the dendritic fields of the hippocampus. Immunoelectron microscopic analysis revealed the overlapping subcellular localization of EFA6A and SNX1 at the post-synaptic density and endosomes in dendritic spines. In Neuro-2a neuroblastoma cells, expression of either EFA6A or SNX1 induced neurite outgrowth, which was further enhanced by co-expression of EFA6A and SNX1. The present findings suggest a novel mechanism by which EFA6A regulates Arf6-mediated neurite formation through the interaction with SNX1.
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