ABSTRACT
Brain-derived neurotrophic factor (BDNF) and its receptors tyrosine kinase receptor B (TrkB) and the p75 neurotrophin receptor (p75) are the primary regulators of dendritic growth in the central nervous system (CNS). After being bound by BDNF, TrkB and p75 are endocytosed into endosomes and continue signaling within the cell soma, dendrites, and axons. We studied the functional role of BDNF axonal signaling in cortical neurons derived from different transgenic mice using compartmentalized cultures in microfluidic devices. We found that axonal BDNF increased dendritic growth from the neuronal cell body in a cAMP response element-binding protein (CREB)-dependent manner. These effects were dependent on axonal TrkB but not p75 activity. Dynein-dependent BDNF-TrkB-containing endosome transport was required for long-distance induction of dendritic growth. Axonal signaling endosomes increased CREB and mTOR kinase activity in the cell body, and this increase in the activity of both proteins was required for general protein translation and the expression of Arc, a plasticity-associated gene, indicating a role for BDNF-TrkB axonal signaling endosomes in coordinating the transcription and translation of genes whose products contribute to learning and memory regulation.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵# Department of Biology, Johns Hopkins University, Baltimore, MD, 21218, USA Email: gmoyaal1{at}jhu.edu.
Funding: The authors gratefully acknowledge financial support from ANID (Agencia Nacional de Investigacion y Desarrollo) FONDECYT (grant N°1171137 and N°1221203) (FCB), the Basal Center of Excellence in Science and Technology (PIA BASAL AFB170005 and ACE210009), CORFO “Consorcio tecnológico desarrollo sinérgico de Ingredientes Funcionales y Aditivos Funcionales IFAN” (16PTECAI-66648) and DGI-UNAB (DI-01-21/NUC) to FCB and a PhD fellowship from CONICYT to GMA.
The manuscript has been shortened and just the main figures maintained.