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Please use this identifier to cite or link to this item: http://hdl.handle.net/1783.1/6174
Title: Endophilin B1 as a novel regulator of nerve growth factor/TrkA trafficking and neurite outgrowth
Authors: Wan, Jun
Cheung, Anthony Yik-Hang
Fu, Wing Yu
Wu, Chengbiao
Zhang, Mingjie
Mobley, William C.
Cheung, Zelda H.
Ip, Nancy Y.
Keywords: Neurotrophin
Trk receptors
Receptor tyrosine kinase
Receptor trafficking
Neurite outgrowth
Endosomes
Issue Date: 3-Sep-2008
Citation: Journal of neuroscience, September 3, 2008, v. 28, no. 36, p. 9002-9012
Abstract: Neurotrophins and their cognate receptors Trks are important regulators of neuronal survival and differentiation. Recent studies reveal that internalization and trafficking of Trks play a critical role in neurotrophin-mediated signaling. At present, little is known of the molecular events that mediate this process. In the current study, we show that endophilin B1 is a novel regulator of nerve growth factor (NGF) trafficking.Wefound that endophilin B1 interacts with both TrkA and early endosome marker EEA1. Interestingly, knockdown of endophilin B1 results in enlarged EEA1-positive vesicles in NGF-treated PC12 cells. This is accompanied by increased lysosomal targeting of NGF/TrkA and TrkA degradation, and reduced total TrkA levels. In addition, knockdown of endophilin B1 attenuates Erk1/2 activation in the endosomal fraction after NGF treatment. This is accompanied by a marked inhibition of NGF-induced gene transcription and neurite outgrowth in endophilin B1-knocked down cells. Our observations implicate endophilin B1 as a novel regulator of NGF trafficking, thereby affecting TrkA levels and downstream signaling on endosomes to mediate biological functions of NGF.
Rights: The Society for Neuroscience is the copyright holder for the work.
URI: http://hdl.handle.net/1783.1/6174
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