Related Experiment Video
Updated: May 6, 2026
10:43
Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
Published on: May 19, 2016
6.2K
Inhibitory signalling to the Arp2/3 complex steers cell migration.
Irene Dang1, Roman Gorelik, Carla Sousa-Blin
11] Group Cytoskeleton in Cell Morphogenesis, Laboratoire d'Enzymologie et Biochimie Structurales, CNRS UPR3082, Gif-sur-Yvette 91190, France [2].
Nature
|October 18, 2013
Summary
A newly discovered protein, Arpin, acts as an inhibitor of the Arp2/3 complex, crucial for cell migration. Its depletion enhances cell speed and directional persistence, revealing a key regulator of cell movement directionality.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Cell migration is essential for development and disease, relying on dynamic actin networks for plasma membrane protrusion in lamellipodia.
- The Arp2/3 complex nucleates branched actin networks, and its activation by WAVE proteins, downstream of Rac GTPase, drives lamellipodia formation.
- Mechanisms governing the directionality of cell migration remain incompletely understood.
Purpose of the Study:
- To identify novel regulators of cell migration directionality.
- To characterize the function of a newly identified protein, Arpin, in the context of cell migration.
- To elucidate the interplay between Arpin and known pathways like Rac-WAVE-Arp2/3 in controlling cell movement.
Main Methods:
- In vitro biochemical assays to determine Arpin's inhibitory effect on the Arp2/3 complex.
- Depletion studies (e.g., using siRNA) in mammalian cells to assess Arpin's role in cell migration speed and directionality.
- Microinjection experiments in fish keratocytes to observe the effects of Arpin manipulation on cell turning behavior.
- Studies in Dictyostelium discoideum to confirm conserved roles of Arpin.
Main Results:
- Arpin was identified as an inhibitor of the Arp2/3 complex in vitro.
- Rac signaling recruits and activates Arpin at the lamellipodial tip, similar to WAVE.
- Depletion of Arpin led to increased lamellipodia protrusion speed and overall cell migration speed.
- Arpin depletion resulted in straighter cell migration trajectories in mammalian cells and Dictyostelium.
- Arpin microinjection induced turning behavior in highly persistent fish keratocyte migration.
Conclusions:
- Arpin acts as a Rac-activated inhibitor of the Arp2/3 complex, playing a critical role in regulating cell migration.
- The balance between the Arpin inhibitory pathway and the WAVE activatory pathway is crucial for controlling cell migration directionality and persistence.
- Arpin represents a conserved mechanism for steering cell movement across different species and cell types.
Related Concept Videos
01:09Cell Migration
16.6K
Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.
16.6K
01:19Cell Migration
6.1K
Cell migration is a process by which the cells move from one location to another, playing an essential role in embryological development, repair and regeneration, immune response, and metastasis. Cells migrate in response to chemical or mechanical signals generated by specific organs or tissues. The overall mechanism includes three steps - polarization, protrusion, and release. Polarization involves the formation of a distinct cell front and rear, which determines the direction of movement.
6.1K
01:21Cell Polarization by Rho Proteins
3.2K
Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
3.2K
01:17Intracellular Signaling Affects Focal Adhesions
2.8K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.8K
01:32Cytoskeletal Coordination in Cell Migration
4.9K
A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
4.9K
01:18Role of Myosin in Cell Migration
2.8K
Myosins are multimeric motor proteins involved in various cellular processes such as migration, adhesion, and proliferation. Myosin II is the most common type in animal cells, which binds and cross-links actin filaments.
Myosin II is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, two regulatory light chains, and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction....
Myosin II is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, two regulatory light chains, and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction....
2.8K