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Journal of the Reticuloendothelial... Jun 1968
Topics: Cell Membrane; Chemical Phenomena; Chemistry; Culture Techniques; Lysosomes; Macrophages; Peptides; Pinocytosis; Proteins; Serum Albumin, Radio-Iodinated
PubMed: 5673752
DOI: No ID Found -
Traffic (Copenhagen, Denmark) Apr 2009Macropinocytosis represents a distinct pathway of endocytosis in mammalian cells. This actin-driven endocytic process is not directly co-ordinated by the presence of... (Review)
Review
Macropinocytosis represents a distinct pathway of endocytosis in mammalian cells. This actin-driven endocytic process is not directly co-ordinated by the presence of cargo but can be induced upon activation of growth factor signalling pathways. The capacity to dissect the contribution of macropinocytosis to cellular processes has been hampered by a lack of unique molecular markers and defining features. While aspects of macropinosome formation and maturation are common to those shared by the other endocytic pathways, a number of key differences have recently begun to emerge and will be discussed in this study. It is now well established that macropinocytosis significantly contributes to antigen presentation by the immune system and is exploited by a range of pathogens for cellular invasion and avoidance of immune surveillance.
Topics: Animals; Antigen Presentation; Bacteria; Drug Delivery Systems; Endocytosis; Endosomes; Pinocytosis; Signal Transduction; Viruses
PubMed: 19192253
DOI: 10.1111/j.1600-0854.2009.00878.x -
Philosophical Transactions of the Royal... Feb 2019Macropinocytosis is an evolutionarily conserved form of endocytosis that mediates non-selective uptake of extracellular fluid and the solutes contained therein. In... (Review)
Review
Macropinocytosis is an evolutionarily conserved form of endocytosis that mediates non-selective uptake of extracellular fluid and the solutes contained therein. In mammalian cells, macropinocytosis is initiated by growth factor-mediated activation of the Ras and PI3-kinase signalling pathways. In malignant cells, oncogenic activation of growth factor signalling sustains macropinocytosis cell autonomously. Recent studies of cancer metabolism, discussed here, have begun to define a role for macropinocytosis as a nutrient uptake route. Macropinocytic cancer cells ingest macromolecules in bulk and break them down in the lysosome to support metabolism and macromolecular synthesis. Thereby, macropinocytosis allows cells to tap into the copious nutrient stores of extracellular macromolecules when canonical nutrients are scarce. These findings demonstrate that macropinocytosis promotes metabolic flexibility and resilience, which enables cancer cells to survive and grow in nutrient-poor environments. Implications for physiological roles of growth factor-stimulated macropinocytosis in cell metabolism and its relationship with other nutrient uptake pathways are considered. This article is part of the Theo Murphy meeting issue 'Macropinocytosis'.
Topics: Animals; Humans; Intercellular Signaling Peptides and Proteins; Neoplasms; Pinocytosis; Signal Transduction
PubMed: 30967008
DOI: 10.1098/rstb.2018.0285 -
Essays in Biochemistry Oct 2019Migration of cells is required in multiple tissue-level processes, such as in inflammation or cancer metastasis. Endocytosis is an extremely regulated cellular process... (Review)
Review
Migration of cells is required in multiple tissue-level processes, such as in inflammation or cancer metastasis. Endocytosis is an extremely regulated cellular process by which cells uptake extracellular molecules or internalise cell surface receptors. While the role of endocytosis of focal adhesions (FA) and plasma membrane (PM) turnover at the leading edge of migratory cells is wide known, the contribution of endocytic proteins per se in migration has been frequently disregarded. In this review, we describe the novel functions of the most well-known endocytic proteins in cancer cell migration, focusing on clathrin, caveolin, flotillins and GRAF1. In addition, we highlight the relevance of the macropinocytic pathway in amoeboid-like cell migration.
Topics: Animals; Caveolin 1; Cell Membrane; Cell Movement; Clathrin; GTPase-Activating Proteins; Humans; Membrane Proteins; Pinocytosis
PubMed: 31350382
DOI: 10.1042/EBC20190014 -
The Journal of Cell Biology Jun 1983Intracellular degradation of exogenous (serum) proteins provides a source of amino acids for cellular protein synthesis. Pinocytosis serves as the mechanism for...
Intracellular degradation of exogenous (serum) proteins provides a source of amino acids for cellular protein synthesis. Pinocytosis serves as the mechanism for delivering exogenous protein to the lysosomes, the major site of intracellular degradation of exogenous protein. To determine whether the availability of extracellular free amino acids altered pinocytic function, we incubated monolayers of pulmonary alveolar macrophages with the fluid-phase marker, [14C]sucrose, and we dissected the pinocytic process by kinetic analysis. Additionally, intracellular degradation of endogenous and exogenous protein was monitored by measuring phenylalanine released from the cell monolayers in the presence of cycloheximide. Results revealed that in response to a subphysiological level of essential amino acids or to amino acid deprivation, (a) the rate of fluid-phase pinocytosis increased in such a manner as to preferentially increase both delivery to and size of an intracellular compartment believed to be the lysosomes, (b) the degradation of exogenously supplied albumin increased, and (c) the fraction of phenylalanine derived from degradation of exogenous albumin and reutilized for de novo protein synthesis increased. Thus, modulation of the pinosome-lysosome pathway may represent a homeostatic mechanism sensitive to the availability of extracellular free amino acids.
Topics: Amino Acids; Animals; Cycloheximide; Exocytosis; Guinea Pigs; Lung; Phenylalanine; Pinocytosis; Proteins; Rabbits; Serum Albumin, Bovine; Sucrose
PubMed: 6853596
DOI: 10.1083/jcb.96.6.1586 -
Philosophical Transactions of the Royal... Feb 2019Macropinosome formation occurs as a localized sequence of biochemical activities and associated morphological changes, which may be considered a form of signal... (Review)
Review
Macropinosome formation occurs as a localized sequence of biochemical activities and associated morphological changes, which may be considered a form of signal transduction leading to the construction of an organelle. Macropinocytosis may also convey information about the availability of extracellular nutrients to intracellular regulators of metabolism. Consistent with this idea, activation of the metabolic regulator mechanistic target of rapamycin complex-1 (mTORC1) in response to acute stimulation by growth factors and extracellular amino acids requires internalization of amino acids by macropinocytosis. This suggests that macropinocytosis is necessary for mTORC1-dependent growth of metazoan cells, both as a route for delivery of amino acids to sensors associated with lysosomes and as a platform for growth factor-dependent signalling to mTORC1 via phosphatidylinositol 3-kinase (PI3K) and the Akt pathway. Because the biochemical signals required for the construction of macropinosomes are also required for cell growth, and inhibition of macropinocytosis inhibits growth factor signalling to mTORC1, we propose that signalling by growth factor receptors is organized into stochastic, structure-dependent cascades of chemical reactions that both build a macropinosome and stimulate mTORC1. More generally, as discrete units of signal transduction, macropinosomes may be subject to feedback regulation by metabolism and cell dimensions. This article is part of the Theo Murphy meeting issue 'Macropinocytosis'.
Topics: Animals; Cell Proliferation; Endosomes; Humans; Pinocytosis; Signal Transduction
PubMed: 30967006
DOI: 10.1098/rstb.2018.0157 -
The Journal of Gene Medicine Feb 2004Pathogen entry into cells occurs by direct penetration of the plasma membrane, clathrin-mediated endocytosis, caveolar endocytosis, pinocytosis or macropinocytosis. For... (Review)
Review
Pathogen entry into cells occurs by direct penetration of the plasma membrane, clathrin-mediated endocytosis, caveolar endocytosis, pinocytosis or macropinocytosis. For a particular agent, the infectious pathways are typically restricted, reflecting a tight relationship with the host. Here, we survey the uptake process of human adenovirus (Ad) type 2 and 5 and integrate it into the cell biology of endocytosis. Ad2 and Ad5 naturally infect respiratory epithelial cells. They bind to a primary receptor, the coxsackie virus B Ad receptor (CAR). The CAR-docked particles activate integrin coreceptors and this triggers a variety of cell responses, including endocytosis. Ad2/Ad5 endocytosis is clathrin-mediated and involves the large GTPase dynamin and the adaptor protein 2. A second endocytic process is induced simultaneously with viral uptake, macropinocytosis. Together, these pathways are associated with viral infection. Macropinocytosis requires integrins, F-actin, protein kinase C and small G-proteins of the Rho family, but not dynamin. Macropinocytosis per se is not required for viral uptake into epithelial cells, but it appears to be a productive entry pathway of Ad artificially targeted to the high-affinity Fcgamma receptor CD64 of hematopoietic cells lacking CAR. In epithelial and hematopoietic cells, the macropinosomal contents are released to the cytosol. This requires viral signalling from the surface and coincides with particle escape from endosomes and infection. It emerges that incoming Ad2 and Ad5 distinctly modulate the endocytic trafficking and disrupt selective cellular compartments. These features can be exploited for effective artificial targeting of Ad vectors to cell types of interest.
Topics: Adenoviridae; Adenoviridae Infections; Animals; Cell Membrane; Clathrin; Coxsackie and Adenovirus Receptor-Like Membrane Protein; Endocytosis; Humans; Phagocytosis; Pinocytosis; Receptors, Virus; Respiratory Mucosa
PubMed: 14978758
DOI: 10.1002/jgm.553 -
British Journal of Pharmacology Nov 1984We investigated whether differences in induction or stimulation of pinocytosis by six amino-glycosides reflected reported differences in their nephrotoxicity....
We investigated whether differences in induction or stimulation of pinocytosis by six amino-glycosides reflected reported differences in their nephrotoxicity. Pinocytosis induced by antibiotics, Na+, K+ or Ca2+ was quantified by the number of pinocytotic channels in Amoeba proteus, a cell suitable for the study of the pinocytotic process. The aminoglycosides were potent inducers of pinocytosis. They were effective in the order of their cationic charge: neomycin greater than gentamicin greater than netilmicin = tobramycin greater than kanamycin greater than streptomycin. Factors which reduced the charge of the molecules, i.e. alkaline pH and combination with carbenicillin or heparin, diminished pinocytosis. Like La3+ the antibiotics inhibited Na+ -induced pinocytosis. The order of efficacy was netilmicin greater than gentamicin greater than neomycin. A similar rank order, which is the reverse of the order of nephrotoxicity, was observed for inhibition of Ca2+ -stimulated, Na+ -induced pinocytosis. Netilmicin was also the most potent inhibitor of the Ca2+-induced pinocytosis in cells treated with concanavalin A. Inhibition of Ca2+ -stimulated pinocytosis by netilmicin was reversed by Ca2+, the calcium ionophore A 23187, or 4-aminopyridine. We have shown that several nephrotoxic cations are strong inducers of pinocytosis in the amoeba, that aminoglycosides in Ringer solution induce pinocytosis in the approximate order of their nephrotoxicity and that factors which are known to diminish toxicity reduce pinocytosis. It, therefore, appears that the mechanism of aminoglycoside nephrotoxicity is related to their ability to induce pinocytosis in the amoeba. Low inducing potency and strong Ca2+ -antagonism, as for netilmicin, are qualities which may reduce the tendency of polycationic compounds to damage proximal tubular cells.
Topics: Aminoglycosides; Amoeba; Animals; Anti-Bacterial Agents; Calcimycin; Calcium; Calcium Channel Blockers; Concanavalin A; Egtazic Acid; Hydrogen-Ion Concentration; Pinocytosis; Sodium
PubMed: 6439268
DOI: 10.1111/j.1476-5381.1984.tb16215.x -
Philosophical Transactions of the Royal... Feb 2019In tumour cells, macropinocytosis functions as an amino acid supply route and supports cancer cell survival and proliferation. Initially demonstrated in oncogenic... (Review)
Review
In tumour cells, macropinocytosis functions as an amino acid supply route and supports cancer cell survival and proliferation. Initially demonstrated in oncogenic KRAS-driven models of pancreatic cancer, macropinocytosis triggers the internalization of extracellular proteins via discrete endocytic vesicles called macropinosomes. The incoming protein cargo is targeted for lysosome-dependent degradation, causing the intracellular release of amino acids. These protein-derived amino acids support metabolic fitness by contributing to the intracellular amino acid pools, as well as to the biosynthesis of central carbon metabolites. In this way, macropinocytosis represents a novel amino acid supply route that tumour cells use to survive the nutrient-poor conditions of the tumour microenvironment. Macropinocytosis has also emerged as an entry mechanism for a variety of nanomedicines, suggesting that macropinocytosis regulation in the tumour setting can be harnessed for the delivery of anti-cancer therapeutics. A slew of recent studies point to the possibility that macropinocytosis is a pervasive feature of many different tumour types. In this review, we focus on the role of this important uptake mechanism in a variety of cancers and highlight the main molecular drivers of macropinocytosis in these malignancies. This article is part of the Theo Murphy meeting issue 'Macropinocytosis'.
Topics: Humans; Neoplasms; Pinocytosis; Tumor Microenvironment
PubMed: 30967003
DOI: 10.1098/rstb.2018.0153 -
The Journal of Cell Biology Jul 2021Actin organization underpins conserved functions at the leading edge of cells. In this issue, Yang et al. (2021. J. Cell Biol.https://doi.org/10.1083/jcb.202010096)...
Actin organization underpins conserved functions at the leading edge of cells. In this issue, Yang et al. (2021. J. Cell Biol.https://doi.org/10.1083/jcb.202010096) characterize Leep1 as a bi-functional regulator of migration and macropinocytosis through PIP3 and the Scar/WAVE complex.
Topics: Actins; Pinocytosis
PubMed: 34128957
DOI: 10.1083/jcb.202105141