The origins and evolution of macropinocytosis

Area of Science:

• Cell Biology
• Evolutionary Biology

Background:

• Macropinocytosis involves cells internalizing micrometre-sized droplets into vesicles.
• This process, known for nearly a century, occurs in metazoa and amoebae but not plants or fungi.
• Its evolutionary origin predates the divergence of amoebozoa and opisthokonts, with evidence of secondary loss in fungi.

Purpose of the Study:

• To explore the evolutionary origins and conserved signaling pathways of macropinocytosis.
• To understand the adaptation of macropinocytosis from feeding to antigen presentation in immune cells.
• To investigate the relationship between macropinocytosis and growth-factor signaling.

Main Methods:

• Review of existing literature on macropinocytosis and related cellular processes.
• Analysis of evolutionary relationships and gene loss in different taxa.
• Examination of signaling pathways involving phosphatidylinositol 3-kinase (PI3-kinase), Ras, and Rac.

Main Results:

• Macropinocytosis evolved from ancient feeding structures, co-opted by growth factor signaling via receptors.
• The conserved pathway involves vesicle acidification, fusion with lysosomes, and membrane retrieval.
• Macropinocytic cups are actin-driven structures regulated by signaling patches of PIP3, active Ras, and active Rac.

Conclusions:

• Macropinocytosis has a deep evolutionary history, serving diverse functions from feeding to immune surveillance.
• The process is tightly regulated by actin cytoskeleton dynamics and conserved signaling molecules.
• Understanding macropinocytosis provides insights into cellular evolution and the development of diseases like cancer.