Endocytome profiling uncovers cell-surface protein dynamics underlying neuronal connectivity.

Area of Science:

• Neuroscience
• Proteomics
• Cell Biology

Background:

• Endocytosis actively remodels the neuronal surface proteome.
• The global extent and circuit-level consequences of endocytosis are not fully understood.
• Comprehensive interrogation of cell-surface protein (CSP) dynamics is challenging.

Purpose of the Study:

• To introduce endocytome profiling, a systematic, cell-type-specific approach for mapping CSP dynamics in situ.
• To comprehensively map the endocytic atlas of developing olfactory receptor neuron (ORN) axons.
• To investigate the role of endocytic regulation in neuronal development and circuit formation.

Main Methods:

• Quantitative proteomic analysis of developing ORN axons.
• Development of endocytome profiling for mapping CSP dynamics.
• Multi-omic integration to uncover transcellular signaling.

Main Results:

• Generated an endocytic atlas of over 1,100 proteins in ORN axons.
• Revealed extensive remodeling of the surface proteome during development.
• Demonstrated precise endosome-to-surface ratio balancing for axon pruning and integrity.
• Identified a growth factor regulating ORN axon targeting via endocytic receptor control.

Conclusions:

• Endocytome profiling provides unprecedented access to cell-surface proteome dynamics.
• This approach offers a powerful platform for dissecting proteome remodeling in diverse cell types.
• Endocytic regulation plays a critical role in neuronal development, axon targeting, and circuit formation.