The formation and closure of macropinocytic cups in a model system

Lutton, E. Josiah; Coker, Helena L.E.; Paschke, Peggy; Munn, Christopher J.; King, Jason; Kay, Rob; Bretschneider, Till

doi:10.1101/2022.10.07.511330

Cited by 7 publications

(6 citation statements)

References 63 publications

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“…In addition, we find that when the passive concave component is highly curved, we observe a phase separation within the CMC clusters, whereby the concave CMC forms an internalized spherical invagination. These invaginations are then squeezed at their base by the active forces induced by the convex CMC, and the calculated membrane shape dynamics resembles the observed process of actin-dependent endocytosis (Doherty and McMahon, 2009;Mooren et al, 2012;Moreno-Layseca et al, 2021;Kaplan et al, 2022) and macropinocytosis (Kay, 2021;Mylvaganam et al, 2021;Sønder et al, 2021;Lutton et al, 2022).…”

Section: Membrane Shapes Driven By Mixtures Of Passive Concave and Ac...mentioning

confidence: 82%

Theoretical model of membrane protrusions driven by curved active proteins

Ravid

Penič

Mimori-Kiyosue

et al. 2023

Front. Mol. Biosci.

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Eukaryotic cells intrinsically change their shape, by changing the composition of their membrane and by restructuring their underlying cytoskeleton. We present here further studies and extensions of a minimal physical model, describing a closed vesicle with mobile curved membrane protein complexes. The cytoskeletal forces describe the protrusive force due to actin polymerization which is recruited to the membrane by the curved protein complexes. We characterize the phase diagrams of this model, as function of the magnitude of the active forces, nearest-neighbor protein interactions and the proteins’ spontaneous curvature. It was previously shown that this model can explain the formation of lamellipodia-like flat protrusions, and here we explore the regimes where the model can also give rise to filopodia-like tubular protrusions. We extend the simulation with curved components of both convex and concave species, where we find the formation of complex ruffled clusters, as well as internalized invaginations that resemble the process of endocytosis and macropinocytosis. We alter the force model representing the cytoskeleton to simulate the effects of bundled instead of branched structure, resulting in shapes which resemble filopodia.

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Section: Membrane Shapes Driven By Mixtures Of Passive Concave and Ac...mentioning

confidence: 82%

Theoretical model of membrane protrusions driven by curved active proteins

Ravid

Penič

Mimori-Kiyosue

et al. 2023

Front. Mol. Biosci.

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show abstract

“…In addition, we find that when the passive concave component is highly curved, we observe a phase separation within the CMC clusters, whereby the concave CMC forms an internalized spherical invagination. These invaginations are then squeezed at their base by the active forces induced by the convex CMC, and the calculated membrane shape dynamics resembles the process of actin-dependent endycytosis [17,[58][59][60] and macropinocytosis [34,[61][62][63].…”

Section: Membrane Shapes Driven By Mixtures Of Passive Concave and Ac...mentioning

confidence: 99%

Theoretical model of membrane protrusions driven by curved active proteins

Ravid

Penič

Mimori-Kiyosue

et al. 2023

Preprint

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Eukaryotic cells intrinsically change their shape, by changing the composition of their membrane and by restructuring their underlying cytoskeleton. We present here further studies and extensions of a minimal physical model, describing a closed vesicle with mobile curved membrane protein complexes. The cytoskeletal forces describe the protrusive force due to actin polymerization which is recruited to the membrane by the curved protein complexes. We characterize the phase diagrams of this model, as function of the magnitude of the active forces, nearest-neighbor protein interactions and the proteins spontaneous curvature. It was previously shown that this model can explain the formation of lamellipodia-like flat protrusions, and here we explore the regimes where the model can also give rise to filopodia-like tubular protrusions. We extend the simulation with curved components of both convex and concave species, where we find the formation of complex ruffled clusters, as well as internalized invaginations that resemble the process of endocytosis and macropinocytosis. We alter the force model representing the cytoskeleton to simulate the effects of bundled instead of branched structure, resulting in shapes which resemble filopodia.

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“…Amoeba Dictyostelium discoideum also has degradative macropinosomes considering that macropinocytosis is a way of feeding for this unicellular organism. Dictyostelium and some mammalian macropinosomes arise from membrane protrusions that shape circular ruffles or macropinocytic cups, which close upon fusion of their distal membranes and finally pinch off from the plasma membrane [6–8]. Such extensive remodelling of the plasma membrane is achieved by Arp2/3 complex-nucleated dendritic F-actin network that pushes the membrane outwards [9].…”

Section: Introductionmentioning

confidence: 99%

IqgC is a potent regulator of macropinocytosis in the presence of NF1 and its loading to macropinosomes is dependent on RasG

Putar,

Čizmar,

Chao

et al. 2024

Open Biol.

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RasG is a major regulator of macropinocytosis in Dictyostelium discoideum . Its activity is under the control of an IQGAP-related protein, IqgC, which acts as a RasG-specific GAP (GTPase activating protein). IqgC colocalizes with the active Ras at the macropinosome membrane during its formation and for some time after the cup closure. However, the loss of IqgC induces only a minor enhancement of fluid uptake in axenic cells that already lack another RasGAP, NF1. Here, we show that IqgC plays an important role in the regulation of macropinocytosis in the presence of NF1 by restricting the size of macropinosomes. We further provide evidence that interaction with RasG is indispensable for the recruitment of IqgC to forming macropinocytic cups. We also demonstrate that IqgC interacts with another small GTPase from the Ras superfamily, Rab5A, but is not a GAP for Rab5A. Since mammalian Rab5 plays a key role in early endosome maturation, we hypothesized that IqgC could be involved in macropinosome maturation via its interaction with Rab5A. Although an excessive amount of Rab5A reduces the RasGAP activity of IqgC in vitro and correlates with IqgC dissociation from endosomes in vivo , the physiological significance of the Rab5A–IqgC interaction remains elusive.

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The formation and closure of macropinocytic cups in a model system

Cited by 7 publications

References 63 publications

Theoretical model of membrane protrusions driven by curved active proteins

Theoretical model of membrane protrusions driven by curved active proteins

Theoretical model of membrane protrusions driven by curved active proteins

IqgC is a potent regulator of macropinocytosis in the presence of NF1 and its loading to macropinosomes is dependent on RasG

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