A plasma membrane template for macropinocytic cups

Veltman, Douwe M.; Williams, Thomas D.; Bloomfield, Gareth; Chen, Bi-Chang; Betzig, Eric; Insall, Robert H.; Kay, Robert R.

doi:10.7554/elife.20085

Cited by 163 publications

(286 citation statements)

References 84 publications

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“…Thirdly, macropinocytic cups are not necessarily formed de novo each time. Recent analysis of macropinosome dynamics in Dictyostelium found that cups were frequently produced by the splitting of pre‐existing ones . Similar behaviour has been described for pseudopods, which spontaneously self‐assemble and proliferate by splitting in both amoebae and immune cells .…”

Section: How Do You Construct a Macropinocytic Cup?mentioning

confidence: 57%

“…The Ras family of small GTPases are also important in macropinocytosis. Expression or injection of constitutively activated (oncogenic) Ras is sufficient to induce ruffling and macropinocytosis in fibroblasts and active Ras localises to macropinocytic cups in both macrophages and Dictyostelium . Ras functionally sits between growth factor receptors and activation of class I PI‐3 kinases via their Ras‐binding domains, providing a direct mechanism for stimulated macropinocytosis .…”

Section: Temporal Signals During Cup Formationmentioning

confidence: 99%

“…How SCAR activity and protrusion is restricted to the cup lip, however, is not understood. SCAR is downstream of Rac1, but probes for activated Rac1 indicate a localisation that mirrors active Ras and PI(3,4,5)P 3 – being uniformly present throughout the cup interior in both Dictyostelium and macrophages . Rac1 may therefore be permissive in driving protrusion; however, other as yet unknown signals must be required that either provide positive reinforcement of SCAR recruitment at the lip or suppress it at the cup base.…”

Section: The Spatial Organisation Of Macropinocytic Cupsmentioning

confidence: 99%

“…In macropinosome formation, it has been proposed that this barrier is due to the encircling, actin‐rich ruffle . However, experiments in Dictyostelium indicate that defined patches of Ras and PI(3,4,5)P 3 are still maintained after actin depolymerisation, implying that additional mechanisms are involved . How this is achieved remains elusive and deserves further attention.…”

Section: The Spatial Organisation Of Macropinocytic Cupsmentioning

confidence: 99%

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Drinking problems: mechanisms of macropinosome formation and maturation

2017

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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.

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Section: How Do You Construct a Macropinocytic Cup?mentioning

confidence: 57%

Section: Temporal Signals During Cup Formationmentioning

confidence: 99%

Section: The Spatial Organisation Of Macropinocytic Cupsmentioning

confidence: 99%

Section: The Spatial Organisation Of Macropinocytic Cupsmentioning

confidence: 99%

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Drinking problems: mechanisms of macropinosome formation and maturation

2017

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“…The expanding cup-like protrusions seen in lattice light sheet microscopy (Chen et al, 2014) of randomly migrating vegetative Dictyostelium cells could be explained by propagating STEN waves driving cytoskeletal activity. Consistently, actin binding proteins rim the cup-like structure which is filled with a broader zone of Ras and PI3K activity (Veltman et al, 2016; Pollitt et al, 2006). These structures, referred to as macropinosomes, are abundant in axenic cells which have been selected for fluid uptake (Maniak, 2001).…”

Section: Propagating Sten Waves and The Protrusions That Underlie Motmentioning

confidence: 85%

Excitable Signal Transduction Networks in Directed Cell Migration

Devreotes

Bhattacharya

Edwards

et al. 2017

Annu. Rev. Cell Dev. Biol.

167

168

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While directed migration may have evolved to escape nutrient depletion, it has been adopted for an extensive range of physiological events during development and in the adult. The subversion of these movements results in disease. Though the mechanisms of propulsion and sensing are extremely diverse, most cells move by extending actin-filled protrusions called macropinosomes, pseudopodia, or lamellipodia or by extension of blebs. In addition to motility, directed migration involves polarity and directional sensing. The hundreds of gene products involved in these processes are organized into networks of parallel and interconnected pathways. Many of these components are activated or inhibited coordinately with stimulation and on each spontaneously extended protrusion. Moreover, these networks display hallmarks of excitability, including “all-or-nothing” responsiveness and wave propagation. Cellular protrusions result from signal transduction waves which propagate outwardly from an origin and drive cytoskeletal activity. The range of the propagating waves and hence the size of the protrusions can be altered by lowering or raising the threshold for network activation, with larger and wider protrusions favoring gliding or oscillatory behavior over amoeboid migration. Here, we evaluate the variety of models of excitable networks controlling directed migration and outline critical tests. We also discuss the utility of this emerging view in producing cell migration and in integrating the various extrinsic cues that direct migration.

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Dictyostelium myosin 1F and myosin 1E inhibit actin waves in a lipid‐binding‐dependent and motor‐independent manner

et al. 2020

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Actin waves are F-actin-rich entities traveling on the ventral plasma membrane by the treadmilling mechanism. Actin waves were first discovered and are best characterized in Dictyostelium. Class I myosins are unconventional monomeric myosins that bind lipids through their tails. Dictyostelium has seven class I myosins, six of these have tails (Myo1A-F) while one has a very short tail (Myo1K), and three of them (Myo1D, Myo1E and Myo1F) bind PIP3 with high affinity. Localization of five Dictyostelium Class I myosins synchronizes with localization and propagation of actin waves. Myo1B and Myo1C colocalize with actin in actin waves, whereas Myo1D, E and F localize to the PIP3-rich region surrounded by actin waves. Here, we studied the effect of overexpression of the three PIP3 specific Class I myosins on actin waves. We found that ectopic expression of the short-tail Myo1F inhibits wave formation, short-tail Myo1E has similar but weaker inhibitory effect, but long-tail Myo1D does not affect waves. A study of Myo1F mutants shows that its membrane-binding site is absolutely required for wave inhibition, but the head portion is not. The results suggest that PIP3 specificity and the presence of two membrane-binding sites are required for inhibition of actin waves, and that inhibition may be caused by crosslinking of PIP3 heads groups.

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A plasma membrane template for macropinocytic cups

Cited by 163 publications

References 84 publications

Drinking problems: mechanisms of macropinosome formation and maturation

Drinking problems: mechanisms of macropinosome formation and maturation

Excitable Signal Transduction Networks in Directed Cell Migration

Dictyostelium myosin 1F and myosin 1E inhibit actin waves in a lipid‐binding‐dependent and motor‐independent manner

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