Macropinosomes are a type of

cellular compartment Cellular compartments in cell biology comprise all of the closed parts within the cytosol of a eukaryotic cell, usually surrounded by a single or double lipid layer membrane. These compartments are often, but not always, defined as membrane-bo ...

that form as a result of

macropinocytosis In cellular biology, pinocytosis, otherwise known as fluid endocytosis and bulk-phase pinocytosis, is a mode of endocytosis in which small molecules dissolved in extracellular fluid are brought into the cell through an invagination of the cell me ...

Formation

Macropinosomes have been described to form via a wave-like mechanism or via a tent-pole formation both of which processes require rapid polymerisation of

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ov ...

-rich structures that rise up from the cell surface before collapsing back down into a macropinosome.

Function

Macropinosomes serve primarily in the uptake of

solutes In chemistry, a solution is a special type of homogeneous mixture composed of two or more substances. In such a mixture, a solute is a substance dissolved in another substance, known as a solvent. If the attractive forces between the solven ...

from the extracellular fluid. Once inside the cell, macropinosomes undergo a process of maturation characterized by increasing expression of

Rab7 Ras-related protein Rab-7a is a protein that in humans is encoded by the ''RAB7A'' gene. Ras-related protein Rab-7a is involved in endocytosis, which is a process that brings substances into a cell. The process of endocytosis works by folding th ...

as they progress through the endocytic pathway, until they fuse with lysosomes where the contents of the macropinosome are degraded.

Regulation

PI3K Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which i ...

and

phosphoinositide phospholipase C Phosphoinositide phospholipase C (PLC, EC 3.1.4.11, triphosphoinositide phosphodiesterase, phosphoinositidase C, 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase, monophosphatidylinositol phosphodiesterase, phosphatidylinositol phosph ...

activation have been shown to be necessary for macropinosome formation in fibroblasts. Members of the SNX family have also been shown to be important in macropinosome formation. Conversely, cyclic AMP has been shown to promote regurgitation from macropinosomes.

Role in pathogenesis

Because the process of macropinocytosis is non-specific, many pathogens take advantage of macropinosomes to infect their target cells. In this way, pathogens internalized in macropinosomes avoid barriers and obstructions that the plasma membrane, cytoplasmic crowding and cortical cytoskeleton pose when moving deeper into the cytoplasm. One example is Ebola virus, responsible for the devastating

ebola virus disease Ebola, also known as Ebola virus disease (EVD) and Ebola hemorrhagic fever (EHF), is a viral hemorrhagic fever in humans and other primates, caused by ebolaviruses. Symptoms typically start anywhere between two days and three weeks after becom ...

, which stimulates macropinosome formation upon binding to the target cell surface.

Vaccinia virus ''Vaccinia virus'' (VACV or VV) is a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, which encodes approximately 250 genes. The dimensions of the v ...

(VACV), a member of poxvirus family, has also been shown to partially utilize macropinocytosis for infectious cell entry. Here, both infectious forms of VACV, mature virion (MV) and enveloped virion (EV), induce their own macropinocytosis by binding to the cell surface and triggering an actin-mediated plasma membrane protrusion that eventually collapses back onto the plasma membrane sealing the attached virion inside a macropinosome, which then goes through a maturation program that leads to core activation and genome release.

Shiga toxin Shiga toxins are a family of related toxins with two major groups, Stx1 and Stx2, expressed by genes considered to be part of the genome of lambdoid prophages. The toxins are named after Kiyoshi Shiga, who first described the bacterial origi ...

produced by

enterohemorrhagic Shigatoxigenic ''Escherichia coli'' (STEC) and verotoxigenic ''E. coli'' (VTEC) are strains of the bacterium ''Escherichia coli'' that produce Shiga toxin (or verotoxin). Only a minority of the strains cause illness in humans. The ones that do ...

''E. coli'' has been shown to enter target cells via macropinocytosis, causing gastrointestinal tract complications. Other pathogens that have been shown to utilize this mechanism are Kaposi's sarcoma-associated herpesvirus and '' Salmonella''.

References

{{Reflist Cell anatomy