Making cups and rings: the 'stalled-wave' model for macropinocytosis

Area of Science:

• Cell Biology
• Biophysics
• Molecular Biology

Background:

• Macropinocytosis is a conserved cellular process for engulfing large fluid volumes.
• Its roles in immunity, disease, and pathogen invasion are significant but mechanisms remain unclear.
• Understanding macropinocytosis is crucial for therapeutic development and basic science.

Purpose of the Study:

• To elucidate the mechanisms of macropinocytic cup formation and closure.
• To present a new model for macropinocytosis based on recent imaging data.

Main Methods:

• Lattice light-sheet microscopy in Dictyostelium amoebae.
• Observation of membrane domains (PIP3, Ras, Rac) and actin polymerization.
• Computational modeling to test the proposed mechanism.

Main Results:

• A 'stalled-wave' model for macropinocytosis is proposed.
• PIP3 and active Ras/Rac domains recruit actin polymerization activators.
• Actin polymerization rings shape and close macropinocytic cups; no coat proteins needed.

Conclusions:

• Actin polymerization rings around dynamic membrane domains are sufficient for macropinocytosis.
• The 'stalled-wave' model provides a framework for understanding this fundamental process.
• This mechanism may be broadly conserved across species and cell types.