Locally Activating TrkB Receptor Generates Actin Waves and Specifies Axonal Fate

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• Actin waves, rich in filamentous actin (F-actin), originate in the somato-neuritic region and propagate towards neurite tips.
• The upstream signals initiating actin waves remain largely unknown.
• Neuronal polarization involves distinguishing between minor and major neurites to establish axonal and dendritic fates.

Purpose of the Study:

• To investigate the upstream cues that initiate actin waves.
• To explore the role of TrkB receptor activation in actin wave generation and neurite elongation.
• To elucidate the molecular mechanisms underlying TrkB-mediated neuronal polarization.

Main Methods:

• Utilized an optogenetic approach (Opto-cytTrkB) for localized TrkB receptor activation.
• Investigated the spatial and functional connections between TrkB signaling, Rac1 pathways, and ankyrinG localization.
• Observed changes in neurite morphology and characteristics following TrkB activation.

Main Results:

• Local TrkB receptor activation at the neurite end successfully initiated actin waves and promoted neurite elongation.
• Activated TrkB signaling in the distal neurite was functionally linked to proximal Rac1 localization and signaling.
• TrkB activation altered ankyrinG localization, inducing axonal characteristics in the stimulated neurite.

Conclusions:

• Local Opto-cytTrkB activation is sufficient to initiate actin waves and trigger neurite elongation.
• TrkB signaling orchestrates a cascade involving Rac1 and ankyrinG to drive neurite development and polarization.
• This study identifies a novel mechanism where actin wave generation by TrkB signaling switches minor neurites to major axonal neurites during neuronal polarization.