RGD Reference Report - Endophilin B1 as a novel regulator of nerve growth factor/ TrkA trafficking and neurite outgrowth. - Rat Genome Database

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Endophilin B1 as a novel regulator of nerve growth factor/ TrkA trafficking and neurite outgrowth.

Authors: Wan, Jun  Cheung, Anthony Y  Fu, Wing-Yu  Wu, Chengbiao  Zhang, Mingjie  Mobley, William C  Cheung, Zelda H  Ip, Nancy Y 
Citation: Wan J, etal., J Neurosci. 2008 Sep 3;28(36):9002-12. doi: 10.1523/JNEUROSCI.0767-08.2008.
RGD ID: 13504749
Pubmed: (View Article at PubMed) PMID:18768694
DOI: Full-text: DOI:10.1523/JNEUROSCI.0767-08.2008

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. We found 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.


Gene Ontology Annotations    

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Eea1  (early endosome antigen 1)
Ntrk1  (neurotrophic receptor tyrosine kinase 1)
Sh3glb1  (SH3 domain -containing GRB2-like endophilin B1)

Additional Information