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Related Concept Videos

Generation of Straight or Branched Actin Filaments01:14

Generation of Straight or Branched Actin Filaments

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The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
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Actin Polymerization01:42

Actin Polymerization

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Actin polymerization occurs through the head-to-tail association of binding sites on monomeric actin or G-actin to form filamentous or F-actin. The polymerization can be divided into three phases ̶  nucleation, elongation, and steady-state phase.
The nucleation phase involves forming a stable nucleus consisting of three actin monomers to form a new actin filament. Actin-binding proteins such as formins and Arp2/3 complex help filament growth post-nucleation. The Formins form straight...
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Mechanism of Lamellipodia Formation01:31

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Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
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Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

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Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
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Formation of Higher-order Actin Filaments01:11

Formation of Higher-order Actin Filaments

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The polymerization of G-actin monomers into filamentous F-actin is a multi-step process. Once the F-actins are formed, they can bundle together in different arrangements to form higher-order networks and regulate cellular functions. Common examples include the formation of lamellipodia and filopodia at the cell's leading edge by actin reorganization in a migrating cell. The microvilli on the brush border epithelial cells are also formed through the F-actin network.
The high-order actin...
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Actin Treadmilling01:18

Actin Treadmilling

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Actin filaments undergo polymerization and depolymerization from either end. The polymerization and depolymerization rates depend on the cytosolic concentration of free G-actins. The polymerization rate is generally higher at the plus or barbed end, while the depolymerization rate is higher at the minus or pointed end. At a steady state, critical concentration describes the concentration of free G-actin monomers at which the polymerization rate at the plus end is equal to that of the...
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Related Experiment Video

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DNA Nanotubes as a Versatile Tool to Study Semiflexible Polymers
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Tunnelling nanotube formation is driven by Eps8/IRSp53-dependent linear actin polymerization.

J Michael Henderson1,2, Nina Ljubojevic1,3, Sevan Belian1,4

  • 1Membrane Traffic and Pathogenesis Unit, Department of Cell Biology and Infection, CNRS UMR 3691, Université de Paris, Institut Pasteur, Paris, France.

The EMBO Journal
|November 27, 2023
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Summary

Tunnelling nanotubes (TNTs) form via actin extension, exceeding filopodia length. Inhibiting branched actin pathways promotes linear actin growth, favoring TNT formation and intercellular communication.

Keywords:
actin cytoskeletoncell biophysicsproteomicstunnelling nanotubes

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Using Microfluidics and Fluorescence Microscopy to Study the Assembly Dynamics of Single Actin Filaments and Bundles
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Area of Science:

  • Cell Biology
  • Cytoskeleton Dynamics
  • Intercellular Communication

Background:

  • Tunnelling nanotubes (TNTs) are actin-based cell structures facilitating intercellular communication.
  • The mechanisms governing TNT formation and their length regulation beyond filopodia remain unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms of TNT formation and length control.
  • To identify key regulators of actin polymerization in TNTs.

Main Methods:

  • Micropatterning and advanced microscopy techniques.
  • Optical tweezer-based force measurements.
  • Proteomic analysis and protein interaction studies.

Main Results:

  • TNTs extend via outward actin polymerization, achieving lengths greater than filopodia.
  • Branched actin pathways (Arp2/3-dependent) limit TNT length and occurrence.
  • Inhibition of Arp2/3 enhances TNT formation by favoring linear actin polymerization, involving Eps8 and IRSp53.

Conclusions:

  • TNT formation is regulated by the balance between branched and linear actin polymerization pathways.
  • Eps8 and IRSp53 play crucial roles in TNT formation by promoting linear actin growth.
  • Targeting these pathways could modulate TNT-mediated intercellular communication.