A receptor-independent signaling pathway for BDNF
Fath, J.; Brouillard, F.; Cabaye, A.; Claverie, D.; Nuss, P.; Poillerat, V.; Chwetzoff, S.; Bouceba, T.; Bouvier, E.; Salameh, M.; Molet, J.; Padilla-Ferrer, A.; Couvert, P.; Acher, F.; Golinelli-Cohen, M.-P.; Chassaing, G.; Trugnan, G.; bernard, c.; Benoliel, J.-J.; Becker, C.
Show abstract
In addition to its well-known receptor-mediated function in cell survival, differentiation and growth, we report that the extracellular brain-derived neurotrophic factor (BDNF) also controls the intracellular KEAP1-NRF2 cytoprotective system by a receptor-independent pathway. Extracellular BDNF can cross the cell membrane as it possesses a protein-translocation domain, also known as cell-penetrating peptide. This membrane crossing process is energy-independent, ruling out endocytosis and receptor-dependent mechanisms. Once in the cytosol, BDNF binds to KEAP1 with a nanomolar affinity, enabling nuclear translocation of NRF2 and transcription of NRF2-target genes. BDNF is thus a major regulator of NRF2 activation. A dysfunction of this BDNF-KEAP1-NRF2 pathway may be involved in most diseases where antioxidant and cytoprotective functions are altered. This novel form of communication, whereby a receptor ligand protein exerts a biological activity by crossing the cell membrane, opens new avenues for cell signaling.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Impaired bidirectional communication between interneurons and oligodendrocyte precursor cells affects cognitive behavior 96%
- Phosphorylation triggers presynaptic phase separation of Liprin-α3 to control active zone structure 96%
- Structure of a lasso peptide bound ETB receptor provides insights into the mechanism of GPCR inverse agonism 96%
Similar papers in this journal
- Unexpected contributions of striatal projection neurons coexpressing dopamine D1 and D2 receptors in balancing motor control 95%
- A hypothalamus-brainstem circuit governs the prioritization of safety over essential needs 95%
- Comparative molecular landscapes of immature neurons in the mammalian dentate gyrus across species reveal special features in humans 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.