Optical Activation of TrkB Signaling

Area of Science:

• Neuroscience
• Molecular Biology
• Optogenetics

Background:

• Brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB) are crucial for neuronal development and survival.
• Dysregulation of TrkB signaling is linked to neurodegenerative diseases and cancer.
• Precise spatiotemporal control of TrkB signaling is needed to understand its dynamic roles.

Purpose of the Study:

• To develop novel optogenetic tools for precise spatial and temporal activation of TrkB signaling.
• To investigate the downstream effects of light-induced TrkB activation.
• To compare different optogenetic strategies for TrkB activation efficiency.

Main Methods:

• Engineered optogenetic systems using Arabidopsis thaliana cryptochrome 2 and aureochrome 1 LOV domain.
• Light-induced homo-dimerization of TrkB intracellular domain in cytosol and on plasma membrane.
• Assessed downstream signaling pathways (MAPK/ERK, PI3K/Akt) and neurite outgrowth in PC12 cells.

Main Results:

• Light-inducible TrkB activation was achieved using cryptochrome 2 and LOV domain systems.
• Optogenetic TrkB activation triggered downstream signaling and neurite outgrowth.
• The cryptochrome 2 approach, inducing cell membrane recruitment and homo-interaction, proved most efficient.

Conclusions:

• Developed versatile optogenetic tools for precise control of TrkB signaling using light.
• These tools enable detailed investigation of BDNF/TrkB pathway dynamics in physiological and pathological contexts.
• The cryptochrome 2-based system offers a highly efficient method for optogenetic TrkB activation.