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Endocytosis reshapes neuronal surfaces, with new profiling mapping over 1,100 cell-surface proteins. This reveals precise control over axon development and targeting through protein dynamics.

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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.