Related Experiment Video
Updated: Apr 4, 2026
12:52
Micromanipulation Techniques Allowing Analysis of Morphogenetic Dynamics and Turnover of Cytoskeletal Regulators
Published on: May 12, 2018
10.6K
Chronophin coordinates cell leading edge dynamics by controlling active cofilin levels
Violaine Delorme-Walker1, Ji-Yeon Seo1, Antje Gohla2
1Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037; Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037;
Summary
Chronophin (CIN) controls cell protrusion force by regulating cofilin activity at the cell edge. This actin regulator is essential for persistent membrane extension and cell migration in carcinoma cells.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Cofilin regulates actin dynamics crucial for cell locomotion.
- Signaling pathways for cell direction are known, but protrusion force mechanisms are unclear in carcinoma cells.
Purpose of the Study:
- To elucidate the molecular machinery generating protrusion force in carcinoma cells.
- To investigate the role of chronophin (CIN) in regulating cofilin activity and cell protrusion.
Main Methods:
- Studied cofilin phosphatase chronophin (CIN) in MTLn3 cells.
- Investigated CIN translocation and cofilin activation after EGF stimulation.
- Analyzed effects on actin dynamics, membrane protrusion, and cell migration.
Main Results:
- CIN spatiotemporally regulates cofilin activity at the cell edge, generating persistent membrane extension.
- CIN translocates to the leading edge in a PI3-kinase, Rac1, and cofilin-dependent manner.
- CIN activation of cofilin promotes actin barbed end formation, accelerates actin turnover, and enhances membrane protrusion.
Conclusions:
- CIN is crucial for balancing protrusion/retraction events during cell migration.
- CIN coordinates leading edge dynamics by controlling active cofilin levels.
- CIN promotes cell protrusion in MTLn3 cells, clarifying a key mechanism of cell locomotion.
Related Concept Videos
01:39Mechanism of Filopodia Formation
3.4K
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...
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...
3.4K
01:32Cytoskeletal Coordination in Cell Migration
5.7K
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...
5.7K
01:21Cell Polarization by Rho Proteins
4.1K
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,...
4.1K
01:45Positive Regulator Molecules
137.2K
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
137.2K
02:39Positive Regulator Molecules
7.1K
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
7.1K
01:19Actin Filament Depolymerization
4.2K
Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins...
In F-actin, the ADF/cofilin proteins...
4.2K