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Pinocytosis00:38

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Cells use energy-requiring bulk transport mechanisms to transfer large particles or large numbers of small particles into or out of the cell. The cells envelop the particles in spherical membranes called vesicles or vacuoles. Vesicles that transport material into the cell are built from the cell membrane. These vesicles encapsulate external molecules and transport them into the cell in a process called endocytosis.
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Cells use energy-requiring bulk transport mechanisms to transfer large particles, or large amounts of small particles, into or out of the cell. The cells envelop the particles in spherical membranes called vesicles or vacuoles. Vesicles that transport material into the cell are built from the cell membrane. These vesicles encapsulate external molecules and transport them into the cell in a process called endocytosis.
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Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
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Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
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A cell's plasma membrane demarcates the cell's borders and determines the nature of its interaction with the environment. Cells exclude certain substances, take in others, and excrete some others in controlled quantities. The plasma membrane must be flexible to allow certain cells, such as red and white blood cells, to change their shape while passing through narrow capillaries. These are the more obvious plasma membrane functions. In addition, the plasma membrane's surface carries...
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A plasma membrane template for macropinocytic cups.

Douwe M Veltman1,2, Thomas D Williams1, Gareth Bloomfield1

  • 1MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.

Elife
|December 14, 2016
PubMed
Summary
This summary is machine-generated.

Cellular uptake via macropinocytosis involves actin rings forming around signaling patches. These patches, containing PIP3, Ras, and Rac, organize actin nucleation for vesicle formation.

Keywords:
SCAR/WAVEactin cytoskeletoncell biologydictyosteliummacropinocytosis

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Macropinocytosis is a cellular process for internalizing large volumes of extracellular fluid via actin-dependent plasma membrane invaginations.
  • The precise molecular organization and regulation of the actin cytoskeleton during macropinocytosis remain incompletely understood.

Purpose of the Study:

  • To investigate the spatial organization of signaling molecules and actin regulators at the plasma membrane during macropinocytosis in Dictyostelium.
  • To elucidate the role of specific signaling pathways, such as Ras and Rac, in the formation and regulation of macropinocytic cups.

Main Methods:

  • Live-cell imaging of fluorescently tagged proteins in Dictyostelium discoideum.
  • Analysis of signaling molecule localization (PIP3, Ras, Rac) and actin dynamics (SCAR/WAVE, F-actin).
  • Genetic manipulation, including mutations in RasGAP NF1, to probe signaling pathways.

Main Results:

  • Macropinocytic cups are organized around co-localized patches of PIP3, active Ras, and active Rac.
  • A ring of active SCAR/WAVE is consistently found at the periphery of these signaling patches and other related structures.
  • Patch formation is independent of the F-actin ring, and Ras signaling plays an instructive role, as evidenced by enlarged patches in NF1 mutants.
  • New macropinocytic cups frequently arise from the splitting of existing cups.

Conclusions:

  • Plasma membrane cup structures, including those in macropinocytosis and phagocytosis, arise from self-organizing signaling patches (Ras/PIP3).
  • These signaling patches recruit actin nucleators to their periphery, driving the formation of the characteristic cup shape.
  • The study proposes a model where signaling patch dynamics, rather than solely actin polymerization, dictate the formation of cellular uptake structures.