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Updated: Jan 1, 2026
Measuring the pH, Redox Chemistries, and Degradative Capacity of Macropinosomes using Dual-Fluorophore Ratiometric Microscopy
Published on: August 19, 2021
Living on soup: macropinocytic feeding in amoebae
Robert R Kay1, Thomas D Williams, James D Manton
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK. rrk@mrc-lmb.cam.ac.uk.
Abstract:
Macropinocytosis is used by a variety of amoebae for feeding on liquid medium. The amoebae project cups and ruffles from their plasma membrane, driven by actin polymerization, and eventually fuse these back to the membrane, entrapping droplets of medium into internal vesicles. These vesicles are of up to several microns in diameter and are processed through the lysosomal digestive system to extract nutrients. Recognizably the same process is used in metazoan cells for a number of medically important purposes, including the pathological growth of cancer cells. We describe the discovery of macropinocytosis in Dictyostelium amoebae, its genetic regulation by the NF1 RasGAP, and the tools available for its investigation. Work on Dictyostelium over the last 30 years has identified many genes that may be important for macropinocytosis, which are listed at dictyBase, and give a basis for mechanistic studies. We argue that the actin cytoskeleton is organized for macropinocytosis by a signalling patch of PIP3 and active Ras and Rac, together with their regulatory proteins and effectors, including the protein kinases Akt and SGK. The Scar/WAVE complex is recruited to the periphery of this patch, triggering the formation of a hollow ring of protrusive actin polymerization, and eventually a macropinocytic cup. Major problems to be addressed include: the dynamics sustaining macropinocytic patches and the mechanism of Scar/WAVE recruitment; the mechanisms of cup closure and of membrane fusion; the ecological situations where amoebae feed by macropinocytosis; and the evolutionary relationship between macropinocytosis and growth factor signalling.
Insights
Macropinocytosis, a feeding process in amoebae, is regulated by NF1 RasGAP in Dictyostelium. This research details its genetic control and molecular mechanisms, offering insights into cell biology and cancer research.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Macropinocytosis is a cellular process used by amoebae for nutrient uptake from liquid media, involving actin-driven membrane projections and vesicle formation.
- This process is conserved in metazoan cells and plays a role in various physiological functions, including pathological conditions like cancer cell growth.
Purpose of the Study:
- To describe the discovery and genetic regulation of macropinocytosis in Dictyostelium.
- To outline available tools for investigating macropinocytosis.
- To elucidate the molecular mechanisms underlying macropinocytosis, including the role of the actin cytoskeleton, signaling pathways, and specific protein complexes.
Main Methods:
- Genetic analysis in Dictyostelium amoebae.
- Biochemical and cell biological approaches to study actin cytoskeleton organization.
- Investigation of signaling pathways involving PIP3, Ras, Rac, Akt, SGK, and the Scar/WAVE complex.
Main Results:
- Identified NF1 RasGAP as a key regulator of macropinocytosis in Dictyostelium.
- Detailed the organization of the actin cytoskeleton by signaling patches of PIP3 and active Ras/Rac.
- Showcased the recruitment of the Scar/WAVE complex to initiate actin polymerization and macropinocytic cup formation.
Conclusions:
- Macropinocytosis in Dictyostelium is a complex process involving coordinated signaling and cytoskeletal dynamics.
- Understanding this process provides a foundation for mechanistic studies and reveals links to metazoan cell functions, including cancer.
- Further research is needed to address key questions regarding the dynamics of signaling patches, cup closure, membrane fusion, ecological roles, and evolutionary connections to growth factor signaling.
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