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

Area of Science:

• Neuroscience
• Cell Biology
• Proteomics

Background:

• Endocytosis is crucial for neuronal function, remodeling the cell surface proteome.
• The global impact of endocytosis on neural circuit development remains poorly understood.

Purpose of the Study:

• To systematically map cell-surface protein dynamics during neural development using a cell-type-specific approach.
• To investigate the role of endocytosis in axon pruning and targeting.

Main Methods:

• Developed endocytome profiling, a quantitative proteomic method.
• Analyzed developing Drosophila olfactory receptor neuron (ORN) axons.
• Integrated multi-omic data.

Main Results:

• Generated an endocytic atlas of over 1,000 proteins.
• Demonstrated precise endosome-to-surface protein ratio regulation for axon pruning and integrity.
• Identified transcellular signaling pathways regulating axon targeting via receptor endocytosis.

Conclusions:

• Endocytome profiling offers unprecedented access to cell-surface proteome dynamics.
• This approach provides a platform for dissecting proteome-scale remodeling in various cell types.
• Endocytosis plays a critical role in orchestrating neural circuit development.