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Detection and Quantification of Tunneling Nanotubes Using 3D Volume View Images
Published on: August 31, 2022
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CCT4 promotes tunneling nanotube formation.
Miyu Enomoto1, Akiko Asada1, Taro Saito1
1Department of Biological Sciences, School of Science, Graduate School of Science, Tokyo Metropolitan University, Japan.
FEBS Letters
|October 17, 2025
Summary
Monomeric CCT4, a protein component, drives the formation of tunneling nanotubes (TNTs) in mammalian cells. These nanotubes, rich in tubulin, facilitate intercellular communication and transport.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Tunneling nanotubes (TNTs) are crucial for intercellular communication.
- The molecular mechanisms governing TNT formation remain incompletely understood.
- T-complex protein 1 subunit delta (CCT4) is known as a component of the TRiC complex and also functions as a monomer.
Purpose of the Study:
- To investigate the role of monomeric CCT4 in the formation of tunneling nanotubes.
- To elucidate the molecular mechanisms by which CCT4 influences TNT structure and dynamics.
Main Methods:
- Expression of GFP-tagged CCT4 proteins in mammalian cultured cells.
- Analysis of nanotube morphology, cytoskeleton composition (actin, tubulin), and mitochondrial content.
- Assessment of microtubule dynamics and intercellular transport via TNTs.
Main Results:
- Monomeric CCT4, not incorporated into the TRiC oligomer, significantly promotes TNT formation.
- These CCT4-induced TNTs contain actin fibers, mitochondria, and are enriched in tubulin.
- Expression of monomeric CCT4 enhances microtubule dynamics and facilitates intercellular CCT4 transport.
Conclusions:
- Monomeric CCT4 possesses a novel function in promoting the formation of thick, microtubule-containing TNTs.
- CCT4 plays a key role in regulating TNT structure and dynamics, influencing cell-to-cell communication.
- This finding expands our understanding of TNT formation mechanisms and the diverse roles of CCT4.
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