Trk retrograde signaling requires persistent, Pincher-directed endosomes

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Signaling

Background:

• Neurotrophins are crucial for neuronal survival and phenotype maintenance.
• Retrograde signaling via Trk-signaling endosomes is vital but poorly understood.
• Identifying the specific retrograde signaling entity is a key challenge.

Purpose of the Study:

• To elucidate the formation, processing, and retrograde transport of Trk-signaling endosomes.
• To compare Trk-endosomal mechanisms with those of the EGF-receptor.
• To identify molecular components involved in Trk-endosome trafficking and signaling.

Main Methods:

• Utilized EGF-bound nanoparticles and chimeric EGF-binding TrkB receptors.
• Investigated endosome formation, processing, and retrograde transport in sympathetic neurons.
• Compared retrograde endosomal signaling pathways of Trk and EGF-receptors.

Main Results:

• Trk and EGF-receptor endosomes exhibit distinct formation and processing mechanisms.
• Both receptor types are retrogradely transported to the soma within multivesicular bodies.
• Trk-multivesicular bodies depend on Pincher-mediated macroendocytosis and resist lysosomal degradation.

Conclusions:

• Pincher-dependent Trk-multivesicular bodies facilitate sustained retrograde signaling.
• This sustained signaling promotes neuronal survival and gene expression.
• Trk signaling pathways are uniquely regulated compared to EGF-receptor pathways.