Macropinocytosis: regulated coordination of endocytic and exocytic membrane traffic events

  title={Macropinocytosis: regulated coordination of endocytic and exocytic membrane traffic events},
  author={Sestina Falcone and Emanuele Cocucci and Paola Podini and Tomas Kirchhausen and Emilio Clementi and Jacopo Meldolesi},
  journal={Journal of Cell Science},
  pages={4758 - 4769}
Macropinocytosis, a form of bulk uptake of fluid and solid cargo into cytoplasmic vacuoles, called macropinosomes, has been studied mostly in relation to antigen presentation. Early membrane traffic events occurring in this process are, however, largely unknown. Using human dendritic cells we show that a marked increase in the rate of macropinocytosis occurs a few minutes after application of two markers (small latex beads or dextran), depends on a slow intracellular Ca2+ concentration ([Ca2+]i… 

Enlargeosome Traffic: Exocytosis Triggered by Various Signals Is Followed by Endocytosis, Membrane Shedding or Both

Depending on the stimulation, the cell‐surface expansion by enlargeosome exocytosis is not always recycled but can induce release of specific membranes, possibly important in the pericellular environment.

The origins and evolution of macropinocytosis

  • J. KingR. Kay
  • Biology
    Philosophical Transactions of the Royal Society B
  • 2018
Growth-factor signalling shares core components with macropinocytosis, based around phosphatidylinositol 3-kinase (PI3-kinases), and it is suggested that it evolved to take control of ancient feeding structures through a coupled growth factor receptor.

The regulated exocytosis of enlargeosomes is mediated by a SNARE machinery that includes VAMP4

VAMP4, an R-SNARE that has never been shown to participate in regulated exocytoses, therefore appears to be harboured in the membrane of enlargeosomes and to be a member of the machinery mediating their regulatedExocytosis.

Non-apoptotic cell death associated with perturbations of macropinocytosis

Examples of cell death associated with dysfunctional macropinocytosis are reviewed and the possibility that small molecules capable of altering macropinosome trafficking or function might be useful as therapeutic agents against cancers that are resistant to drugs that work by inducing apoptosis is raised.

Endocytosis unplugged: multiple ways to enter the cell

This work provides an account of various endocytic routes, their mechanisms of operation and occurrence across phyla, and a description of the functional hierarchy of molecular players in these mechanisms of internalization.

From Pinocytosis to Methuosis—Fluid Consumption as a Risk Factor for Cell Death

Important cellular mechanisms, components, and processes that may lead to methuotic CD upon their derangement are highlighted and various aspects of the complex mutual interplay between extracellular and intracellular ions and ion gradients, the PM and vesicular membrane, phosphoinositides, monomeric G proteins and their targets, as well as the submembranous cytoskeleton are described.

Identification of a developmentally regulated pathway of membrane retrieval in neuronal growth cones

A constitutive, high-capacity plasma-membrane-recycling activity in the axonal growth cones is identified, which is mediated by a novel bulk endocytic pathway that is mechanistically related to macropinocytosis.

Active macropinocytosis induction by stimulation of epidermal growth factor receptor and oncogenic Ras expression potentiates cellular uptake efficacy of exosomes

It is demonstrated the active induction of macropinocytosis (accompanied by actin reorganisation, ruffling of plasma membrane, and engulfment of large volumes of extracellular fluid) by stimulation of cancer-related receptors and show that the epidermal growth factor (EGF) receptor significantly enhances the cellular uptake of exosomes.

Differential Regulation of Macropinocytosis by Abi1/Hssh3bp1 Isoforms

It is demonstrated that Abi1 isoforms 2 and 3 differentially regulate macropinocytosis as a consequence of their different relative affinities for activated Rac1 in Wave 2 complex, which raises the possibility that isoform-specific roles occur in other Abi 1 functions.

A Differential Role for Macropinocytosis in Mediating Entry of the Two Forms of Vaccinia Virus into Dendritic Cells

It is concluded that VACV enters DCs via macropinocytosis, however, MV was consistently less sensitive to inhibition and is likely to utilise at least one other entry pathway.



Origin, originality, functions, subversions and molecular signalling of macropinocytosis.

It is suggested that, in enterocytes that do not normally phagocytose, the P13K-PLC signalling pathway leading to selective induction of macropinocytosis at the luminal surface has been subverted by enteropathogenic bacteria to penetrate via "spacious phagosomes".

Enlargeosome, an exocytic vesicle resistant to nonionic detergents, undergoes endocytosis via a nonacidic route.

Specific aspects of enlargeosomes are defined and suggested their participation, in addition to cell differentiation and repair, to other physiological and pathological processes are suggested.

Dynamin regulates focal exocytosis in phagocytosing macrophages.

Results suggest that dynamin is involved in the production and/or movement of vesicles from an intracellular organelle to the cell surface to support membrane expansion around the engulfed particle.

The coated pit and macropinocytic pathways serve distinct endosome populations

It is suggested that different endocytic mechanisms can give rise to distinct endosome populations as defined by labeling with transferrin or with LDL.

The endocytic activity of dendritic cells

It is reported that dendritic cells can vigorously internalize solutes by macropinocytosis, delivering these to MHC class II-rich vesicles (MIIVs), where they presumably can be converted to peptides and recycled to the cell surface as MHC II-peptide complexes.

Adenovirus triggers macropinocytosis and endosomal leakage together with its clathrin-mediated uptake

It is concluded that Ad signaling from the cell surface controls the induction of macropinosome formation and leakage, and this correlates with viral exit to the cytosol and infection.

Macropinosome maturation and fusion with tubular lysosomes in macrophages

Macropinosome progress through macrophages showed features of both the maturation and vesicle shuttle models of endocytosis, beginning with a maturation process and ending by merger into a stable, resident lysosomal compartment.

Focal Exocytosis of Vamp3-Containing Vesicles at Sites of Phagosome Formation

It is shown that polarized fusion of VAMP3 vesicles precedes phagosome sealing, and it is likely that targeted delivery of endomembranes contributes to the elongation of pseudopods.


Because macropinosomes are relatively large, they provide an efficient route for non-selective endocytosis of solute macromolecules, this route may facilitate MHC-class-II-restricted antigen presentation by dendritic cells.

Macropinocytosis Is the Endocytic Pathway That Mediates Macrophage Foam Cell Formation with Native Low Density Lipoprotein*

Macropinocytosis of LDL taken up in the fluid phase without receptor-mediated binding of LDL is a novel endocytic pathway that generates macrophage foam cells as a new pathway to target for modulating foam cell formation in atherosclerosis.