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Article ; Online: Dynamic Rac1 inhibition by CYRI helps cells drink, but stops them from driving.

King, Jason S

2021 Volume 220, Issue 9

Abstract: In this issue, Le et al. (2021. J. Cell Biol.https://doi.org/10.1083/jcb.202012114) describe a new role for the recently discovered protein CYRI in controlling the protrusions that allow cells to engulf extracellular fluid by macropinocytosis. This study ...

Abstract	In this issue, Le et al. (2021. J. Cell Biol.https://doi.org/10.1083/jcb.202012114) describe a new role for the recently discovered protein CYRI in controlling the protrusions that allow cells to engulf extracellular fluid by macropinocytosis. This study helps explain how these structures are disassembled, but also uncovers a new mechanism linking the ability of cells to drink and their capacity for invasive migration.
MeSH term(s)	Pinocytosis
Language	English
Publishing date	2021-08-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	218154-x
ISSN	1540-8140 ; 0021-9525
ISSN (online)	1540-8140
ISSN	0021-9525
DOI	10.1083/jcb.202108041
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Article ; Online: Cellular microbiology interview-Dr. Jason King.

King, Jason S

Cellular microbiology

2019 Volume 21, Issue 6, Page(s) e13007

MeSH term(s)	Animals ; Autophagy ; Career Choice ; Dictyostelium/metabolism ; History, 20th Century ; History, 21st Century ; Humans ; Mammals/metabolism ; Phagocytosis ; Pinocytosis ; United Kingdom
Language	English
Publishing date	2019-02-12
Publishing country	England
Document type	Biography ; Historical Article ; Interview ; Portrait
ZDB-ID	1468320-9
ISSN	1462-5822 ; 1462-5814
ISSN (online)	1462-5822
ISSN	1462-5814
DOI	10.1111/cmi.13007
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Zs.A 5288: Show issues

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Article ; Online: Katnip is needed to maintain microtubule function and lysosomal delivery to autophagosomes and phagosomes.

Starling, Georgina P / Phillips, Ben A / Ganesh, Sahana / King, Jason S

Molecular biology of the cell

2023 Volume 34, Issue 3, Page(s) ar12

Abstract: The efficient delivery of lysosomes is essential for many cell functions, such as the degradation of unwanted intracellular components by autophagy and the killing and digestion of extracellular microbes within phagosomes. Using the ... ...

Abstract	The efficient delivery of lysosomes is essential for many cell functions, such as the degradation of unwanted intracellular components by autophagy and the killing and digestion of extracellular microbes within phagosomes. Using the amoeba
MeSH term(s)	Animals ; Autophagosomes ; Dictyostelium/metabolism ; Phagosomes/metabolism ; Lysosomes/metabolism ; Autophagy/genetics ; Microtubules
Language	English
Publishing date	2023-01-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1098979-1
ISSN	1939-4586 ; 1059-1524
ISSN (online)	1939-4586
ISSN	1059-1524
DOI	10.1091/mbc.E22-02-0063
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Zs.A 2853: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Water loss regulates cell and vesicle volume.

King, Jason S / Smythe, Elizabeth

Science (New York, N.Y.)

2020 Volume 367, Issue 6475, Page(s) 246–247

MeSH term(s)	Cell Size ; Cytoplasmic Vesicles ; Lipids ; Water
Chemical Substances	Lipids ; Water (059QF0KO0R)
Language	English
Publishing date	2020-01-16
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.aba3623
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Article ; Online: The endocytic pathways of Dictyostelium discoideum.

Vines, James H / King, Jason S

The International journal of developmental biology

2019 Volume 63, Issue 8-9-10, Page(s) 461–471

Abstract: The formation and processing of vesicles from the cell surface serves many important cellular functions ranging from nutrient acquisition to regulating the turnover of membrane components and signalling. In this article, we summarise the endocytic ... ...

Abstract	The formation and processing of vesicles from the cell surface serves many important cellular functions ranging from nutrient acquisition to regulating the turnover of membrane components and signalling. In this article, we summarise the endocytic pathways of the social amoeba Dictyostelium from the clathrin-dependent and independent internalisation of surface components to the engulfment of bacteria or fluid by phagocytosis and macropinocytosis respectively. Due to similarities with the professional phagocytes of the mammalian immune system Dictyostelium has been extensively used to investigate the complex remodelling and trafficking events that occur as phagosomes and macropinosomes transit through the cell. Here we discuss what is known about this maturation process in order to kill any potential pathogens and obtain nutrients for growth. Finally, we aim to put these studies in evolutionary context and highlight some of the many questions that remain in our understanding of these complex and important pathways.
MeSH term(s)	Cell Membrane/metabolism ; Cell Movement ; Clathrin/metabolism ; Dictyostelium/physiology ; Endocytosis ; Exocytosis ; Immune System ; Lysosomes/metabolism ; Phagocytosis ; Phagosomes/metabolism ; Pinocytosis ; Signal Transduction
Chemical Substances	Clathrin
Language	English
Publishing date	2019-12-12
Publishing country	Spain
Document type	Journal Article ; Review
ZDB-ID	1036070-0
ISSN	1696-3547 ; 0214-6282
ISSN (online)	1696-3547
ISSN	0214-6282
DOI	10.1387/ijdb.190236jk
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Article ; Online: The origins and evolution of macropinocytosis.

King, Jason S / Kay, Robert R

Philosophical transactions of the Royal Society of London. Series B, Biological sciences

2019 Volume 374, Issue 1765, Page(s) 20180158

Abstract: In macropinocytosis, cells take up micrometre-sized droplets of medium into internal vesicles. These vesicles are acidified and fused to lysosomes, their contents digested and useful compounds extracted. Indigestible contents can be exocytosed. ... ...

Abstract	In macropinocytosis, cells take up micrometre-sized droplets of medium into internal vesicles. These vesicles are acidified and fused to lysosomes, their contents digested and useful compounds extracted. Indigestible contents can be exocytosed. Macropinocytosis has been known for approaching 100 years and is described in both metazoa and amoebae, but not in plants or fungi. Its evolutionary origin goes back to at least the common ancestor of the amoebozoa and opisthokonts, with apparent secondary loss from fungi. The primary function of macropinocytosis in amoebae and some cancer cells is feeding, but the conserved processing pathway for macropinosomes, which involves shrinkage and the retrieval of membrane to the cell surface, has been adapted in immune cells for antigen presentation. Macropinocytic cups are large actin-driven processes, closely related to phagocytic cups and pseudopods and appear to be organized around a conserved signalling patch of PIP3, active Ras and active Rac that directs actin polymerization to its periphery. Patches can form spontaneously and must be sustained by excitable kinetics with strong cooperation from the actin cytoskeleton. Growth-factor signalling shares core components with macropinocytosis, based around phosphatidylinositol 3-kinase (PI3-kinase), and we suggest that it evolved to take control of ancient feeding structures through a coupled growth factor receptor. This article is part of the Theo Murphy meeting issue 'Macropinocytosis'.
MeSH term(s)	Amoebozoa/physiology ; Animals ; Biological Evolution ; Humans ; Pinocytosis/physiology ; Signal Transduction/physiology
Language	English
Publishing date	2019-04-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	208382-6
ISSN	1471-2970 ; 0080-4622 ; 0264-3839 ; 0962-8436
ISSN (online)	1471-2970
ISSN	0080-4622 ; 0264-3839 ; 0962-8436
DOI	10.1098/rstb.2018.0158
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Article: The Amoebal Model for Macropinocytosis.

Kay, Robert R / Lutton, Josiah / Coker, Helena / Paschke, Peggy / King, Jason S / Bretschneider, Till

Sub-cellular biochemistry

2022 Volume 98, Page(s) 41–59

Abstract: Macropinocytosis is a relatively unexplored form of large-scale endocytosis driven by the actin cytoskeleton. Dictyostelium amoebae form macropinosomes from cups extended from the plasma membrane, then digest their contents and absorb the nutrients in ... ...

Abstract	Macropinocytosis is a relatively unexplored form of large-scale endocytosis driven by the actin cytoskeleton. Dictyostelium amoebae form macropinosomes from cups extended from the plasma membrane, then digest their contents and absorb the nutrients in the endo-lysosomal system. They use macropinocytosis for feeding, maintaining a high rate of fluid uptake that makes assay and experimentation easy. Mutants collected over the years identify cytoskeletal and signalling proteins required for macropinocytosis. Cups are organized around plasma membrane domains of intense PIP3, Ras and Rac signalling, proper formation of which also depends on the RasGAPs NF1 and RGBARG, PTEN, the PIP3-regulated protein kinases Akt and SGK and their activators PDK1 and TORC2, Rho proteins, plus other components yet to be identified. This PIP3 domain directs dendritic actin polymerization to the extending lip of macropinocytic cups by recruiting a ring of the SCAR/WAVE complex around itself and thus activating the Arp2/3 complex. The dynamics of PIP3 domains are proposed to shape macropinocytic cups from start to finish. The role of the Ras-PI3-kinase module in organizing feeding structures in unicellular organisms most likely predates its adoption into growth factor signalling, suggesting an evolutionary origin for growth factor signalling.
MeSH term(s)	Actin Cytoskeleton/metabolism ; Amoeba/metabolism ; Dictyostelium/genetics ; Dictyostelium/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Pinocytosis
Language	English
Publishing date	2022-04-04
Publishing country	United States
Document type	Journal Article
ISSN	0306-0225 ; 0096-8757
ISSN	0306-0225 ; 0096-8757
DOI	10.1007/978-3-030-94004-1_3
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Article ; Online: Drinking problems: mechanisms of macropinosome formation and maturation.

Buckley, Catherine M / King, Jason S

The FEBS journal

2017 Volume 284, Issue 22, Page(s) 3778–3790

Abstract: Macropinocytosis is a mechanism for the nonspecific bulk uptake and internalisation of extracellular fluid. This plays specific and distinct roles in diverse cell types such as macrophages, dendritic cells and neurons, by allowing cells to sample their ... ...

Abstract	Macropinocytosis is a mechanism for the nonspecific bulk uptake and internalisation of extracellular fluid. This plays specific and distinct roles in diverse cell types such as macrophages, dendritic cells and neurons, by allowing cells to sample their environment, extract extracellular nutrients and regulate plasma membrane turnover. Macropinocytosis has recently been implicated in several diseases including cancer, neurodegenerative diseases and atherosclerosis. Uptake by macropinocytosis is also exploited by several intracellular pathogens to gain entry into host cells. Both capturing and subsequently processing large volumes of extracellular fluid poses a number of unique challenges for the cell. Macropinosome formation requires coordinated three-dimensional manipulation of the cytoskeleton to form shaped protrusions able to entrap extracellular fluid. The following maturation of these large vesicles then involves a complex series of membrane rearrangements to shrink and concentrate their contents, while delivering components required for digestion and recycling. Recognition of the diverse importance of macropinocytosis in physiology and disease has prompted a number of recent studies. In this article, we summarise advances in our understanding of both macropinosome formation and maturation, and seek to highlight the important unanswered questions.
Language	English
Publishing date	2017-11
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.14115
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Article ; Online: A PI(3,5)P2 reporter reveals PIKfyve activity and dynamics on macropinosomes and phagosomes.

Vines, James H / Maib, Hannes / Buckley, Catherine M / Gueho, Aurelie / Zhu, Zhou / Soldati, Thierry / Murray, David H / King, Jason S

The Journal of cell biology

2023 Volume 222, Issue 9

Abstract: Phosphoinositide signaling lipids (PIPs) are key regulators of membrane identity and trafficking. Of these, PI(3,5)P2 is one of the least well-understood, despite key roles in many endocytic pathways including phagocytosis and macropinocytosis. PI(3,5)P2 ...

Abstract	Phosphoinositide signaling lipids (PIPs) are key regulators of membrane identity and trafficking. Of these, PI(3,5)P2 is one of the least well-understood, despite key roles in many endocytic pathways including phagocytosis and macropinocytosis. PI(3,5)P2 is generated by the phosphoinositide 5-kinase PIKfyve, which is critical for phagosomal digestion and antimicrobial activity. However PI(3,5)P2 dynamics and regulation remain unclear due to lack of reliable reporters. Using the amoeba Dictyostelium discoideum, we identify SnxA as a highly selective PI(3,5)P2-binding protein and characterize its use as a reporter for PI(3,5)P2 in both Dictyostelium and mammalian cells. Using GFP-SnxA, we demonstrate that Dictyostelium phagosomes and macropinosomes accumulate PI(3,5)P2 3 min after engulfment but are then retained differently, indicating pathway-specific regulation. We further find that PIKfyve recruitment and activity are separable and that PIKfyve activation stimulates its own dissociation. SnxA is therefore a new tool for reporting PI(3,5)P2 in live cells that reveals key mechanistic details of the role and regulation of PIKfyve/PI(3,5)P2.
MeSH term(s)	Animals ; Dictyostelium/genetics ; Endosomes ; Mammals ; Phagosomes ; Phosphatidylinositols ; Phosphatidylinositol 3-Kinases/metabolism
Chemical Substances	phosphatidylinositol 3,5-diphosphate ; Phosphatidylinositols ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-)
Language	English
Publishing date	2023-06-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218154-x
ISSN	1540-8140 ; 0021-9525
ISSN (online)	1540-8140
ISSN	0021-9525
DOI	10.1083/jcb.202209077
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Article ; Online: Formation and closure of macropinocytic cups in Dictyostelium.

Lutton, Judith E / Coker, Helena L E / Paschke, Peggy / Munn, Christopher J / King, Jason S / Bretschneider, Till / Kay, Robert R

Current biology : CB

2023 Volume 33, Issue 15, Page(s) 3083–3096.e6

Abstract: Macropinocytosis is a conserved endocytic process by which cells engulf droplets of medium into micron-sized vesicles. We use light-sheet microscopy to define an underlying set of principles by which macropinocytic cups are shaped and closed in ... ...

Abstract	Macropinocytosis is a conserved endocytic process by which cells engulf droplets of medium into micron-sized vesicles. We use light-sheet microscopy to define an underlying set of principles by which macropinocytic cups are shaped and closed in Dictyostelium amoebae. Cups form around domains of PIP3 stretching almost to their lip and are supported by a specialized F-actin scaffold from lip to base. They are shaped by a ring of actin polymerization created by recruiting Scar/WAVE and Arp2/3 around PIP3 domains, but how cups evolve over time to close and form a vesicle is unknown. Custom 3D analysis shows that PIP3 domains expand from small origins, capturing new membrane into the cup, and crucially, that cups close when domain expansion stalls. We show that cups can close in two ways: either at the lip, by inwardly directed actin polymerization, or the base, by stretching and delamination of the membrane. This provides the basis for a conceptual mechanism whereby closure is brought about by a combination of stalled cup expansion, continued actin polymerization at the lip, and membrane tension. We test this through the use of a biophysical model, which can recapitulate both forms of cup closure and explain how 3D cup structures evolve over time to mediate engulfment.
MeSH term(s)	Actins ; Dictyostelium ; Cell Membrane Structures ; Actin Cytoskeleton ; Endocytosis
Chemical Substances	Actins
Language	English
Publishing date	2023-06-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1071731-6
ISSN	1879-0445 ; 0960-9822
ISSN (online)	1879-0445
ISSN	0960-9822
DOI	10.1016/j.cub.2023.06.017
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