Related Experiment Video
Updated: Jul 2, 2025
07:53
Analyses of Actin Dynamics, Clutch Coupling and Traction Force for Growth Cone Advance
Published on: October 21, 2021
3.4K
Adhesion-clutch between DCC and netrin-1 mediates netrin-1-induced axonal haptotaxis
Zhen Qiu1, Takunori Minegishi1, Daichi Aoki1
1Laboratory of Systems Neurobiology and Medicine, Division of Biological Science, Nara Institute of Science and Technology, Nara, Japan.
Frontiers in Molecular Neuroscience
|February 20, 2024
Summary
Netrin-1 guides axons via the DCC receptor and shootin1, which link to the cell's internal actin network. This interaction allows growth cones to physically grip and pull on netrin-1 substrates, directing axon growth.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Axon guidance is crucial for neural circuit formation.
- Haptotaxis, guided by substrate-bound cues, is a key axon guidance mechanism.
- Netrin-1 is a known haptotactic cue, but its mechanism is poorly understood.
Purpose of the Study:
- To elucidate the molecular mechanism of netrin-1-induced axonal haptotaxis.
- To investigate the role of the netrin-1 receptor, DCC, and its interaction with shootin1.
Main Methods:
- Utilized speckle imaging to analyze growth cone dynamics.
- Investigated physical interactions between DCC, netrin-1, and adhesive substrates.
- Employed shootin1 knockout models to assess functional consequences.
Main Results:
- Substrate-bound netrin-1 enhances physical interactions between DCC and the substrate.
- DCC exhibits a 'grip' state on netrin-1 substrates, increasing traction force.
- Shootin1 links DCC to actin retrograde flow, mediating force transmission.
- Disruption of the DCC-shootin1 linkage impairs netrin-1-induced haptotaxis.
Conclusions:
- Netrin-1-induced haptotaxis relies on an adhesion-clutch mechanism involving DCC and shootin1.
- This mechanism facilitates asymmetric force generation within the growth cone for directional axon outgrowth.
Related Concept Videos
01:21Chemotaxis and Direction of Cell Migration
3.4K
Cells can detect chemical cues in their environment and reorganize the cytoskeleton to migrate toward them or away from them. This directional migration, called chemotaxis, is essential during embryogenesis and development, immune response, tissue repair and regeneration, and reproduction. These chemical cues can either attract or repel the cell's movement. For example, axon development is determined by a combination of chemoattractants and chemorepellents that direct the growing axon...
3.4K
01:17Intracellular Signaling Affects Focal Adhesions
2.7K
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...
2.7K
01:05Mechanism of Ciliary Motion
3.7K
The ciliary structures were first seen in 1647 by Antonie Leeuwenhoek while observing the protozoans. In lower organisms, these appendages are responsible for cell movement, while in higher organisms, these appendages help in the movement of the extracellular fluids within the body cavities.
The cilia are made up of microtubules in a 9+2 arrangement, with nine microtubule doublet ring bundles, surrounding a pair of central singlet microtubule bundles. The doublet microtubule bundles are...
The cilia are made up of microtubules in a 9+2 arrangement, with nine microtubule doublet ring bundles, surrounding a pair of central singlet microtubule bundles. The doublet microtubule bundles are...
3.7K
01:26Tension Response at Adherens Junctions
2.6K
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
2.6K
01:32Cytoskeletal Coordination in Cell Migration
4.8K
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...
4.8K
01:31Mechanism of Lamellipodia Formation
2.6K
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...
2.6K