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- Title
BDNF/TrkB signaling endosomes in axons coordinate CREB/mTOR activation and protein synthesis in the cell body to induce dendritic growth in cortical neurons.
- Authors
Moya-Alvarado, Guillermo; Tiburcio-Felix, Reynaldo; Ibáñez, María Raquel; Aguirre-Soto, Alejandro A.; Guerra, Miguel V.; Wu, Chengbiao; Mobley, William C.; Perlson, Eran; Bronfman, Francisca C.
- Abstract
Brain- derived neurotrophic factor (BDNF) and its receptors tropomyosin kinase receptor B (TrkB) and the p75 neurotrophin receptor (p75) are the primary regulators of dendritic growth in the 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-TrkBcontaining 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.
- Subjects
MTOR protein; BRAIN-derived neurotrophic factor; NEUROTROPHIN receptors; PROTEIN synthesis; ENDOSOMES; MICROFLUIDIC devices
- Publication
eLife, 2023, p1
- ISSN
2050-084X
- Publication type
Article