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Article Addendum

Endophilin B1

Guarding the gate to destruction

&
Pages 130-132 | Received 28 Dec 2008, Accepted 02 Jan 2009, Published online: 01 Mar 2009

Figures & data

Figure 1 A schematic depicting the potential role of endophilin B1 in NGF/TrkA trafficking and downstream function. Binding of NGF to TrkA triggers internalization of the NGF/TrkA complex through clathrin-mediated endocytosis. Subsequent to clathrin uncoating, the vesicles containing the internalized NGF/TrkA complex fuse with early endosomes, where endophilin B1 interacts and co-localizes extensively with early endosome marker EEA1. Endophilin B1 possibly controls the trafficking of internalized NGF/TrkA from early endosomes to late endosomes, as knock-down of endophilin B1 expression results in premature targeting of TrkA to late endosomes and lysosomes, leading to reduced total TrkA level. Endophilin B1 also appears to facilitate recycling of NGF/TrkA to the cell surface. Nonetheless, whether endophilin B1 regulates endocytosis and the trafficking of NGF/TrkA from plasma membrane to early endosomes remain to be elucidated. Our data suggest that by preventing precocious targeting of NGF/TrkA to the degradation pathway, endophilin B1 preserves TrkA level and contributes to Erk1/2 activation on endosomes, thereby enabling NGF-induced neurite outgrowth.

Figure 1 A schematic depicting the potential role of endophilin B1 in NGF/TrkA trafficking and downstream function. Binding of NGF to TrkA triggers internalization of the NGF/TrkA complex through clathrin-mediated endocytosis. Subsequent to clathrin uncoating, the vesicles containing the internalized NGF/TrkA complex fuse with early endosomes, where endophilin B1 interacts and co-localizes extensively with early endosome marker EEA1. Endophilin B1 possibly controls the trafficking of internalized NGF/TrkA from early endosomes to late endosomes, as knock-down of endophilin B1 expression results in premature targeting of TrkA to late endosomes and lysosomes, leading to reduced total TrkA level. Endophilin B1 also appears to facilitate recycling of NGF/TrkA to the cell surface. Nonetheless, whether endophilin B1 regulates endocytosis and the trafficking of NGF/TrkA from plasma membrane to early endosomes remain to be elucidated. Our data suggest that by preventing precocious targeting of NGF/TrkA to the degradation pathway, endophilin B1 preserves TrkA level and contributes to Erk1/2 activation on endosomes, thereby enabling NGF-induced neurite outgrowth.