# CCT4 promotes tunneling nanotube formation

**Authors:** Miyu Enomoto, Akiko Asada, Taro Saito, Kanae Ando

PMC · DOI: 10.1002/1873-3468.70190 · Febs Letters · 2025-10-17

## TL;DR

This study shows that the protein CCT4 helps form tunneling nanotubes, which are structures that connect cells and allow for communication and transport.

## Contribution

The study identifies a new role for monomeric CCT4 in promoting the formation of microtubule-containing tunneling nanotubes.

## Key findings

- Monomeric CCT4 induces the formation of nanotubes containing actin fibers and mitochondria.
- CCT4 enhances microtubule dynamics and increases tubulin-containing tunneling nanotubes.
- CCT4 proteins are transported intercellularly via the nanotubes they form.

## Abstract

Tunneling nanotubes (TNTs) are membranous tunnel‐like structures that mediate cell‐to‐cell communication, although the molecular mechanisms of TNT formation are not fully understood. T‐complex protein 1 subunit delta (CCT4) serves as a component of the chaperonin‐containing TCP1 complex (TRiC) and also functions as a monomer. Here, we report that monomeric CCT4 promotes TNT formation in mammalian cultured cells. The expression of GFP–CCT4 proteins, which are not incorporated into the chaperonin oligomer, induces the formation of nanotubes containing actin fibers and mitochondria. CCT4 proteins are transported intercellularly via these nanotubes. The expression of monomeric CCT4 enhances microtubule dynamics and increases tubulin‐containing TNTs. Our results suggest a newly identified function of monomeric CCT4 in TNT formation.

Impact statementTunneling nanotubes (TNTs) play critical roles in various physiological and pathological conditions. TNTs vary in their morphology and cytoskeleton. We found that cells expressing monomeric CCT4 generate many thick TNTs with tubulin. Our results suggest that CCT4 drives the formation of microtubule‐containing TNTs.

Tunneling nanotubes (TNTs) play critical roles in various physiological and pathological conditions. TNTs vary in their morphology and cytoskeleton. We found that cells expressing monomeric CCT4 generate many thick TNTs with tubulin. Our results suggest that CCT4 drives the formation of microtubule‐containing TNTs.

Tunneling nanotubes (TNTs) are membranous tunnel‐like structures that transport molecules and organelles between cells. They vary in thickness, and thick nanotubes often contain microtubules in addition to actin fibers. We found that cells expressing monomeric CCT4 generate many thick TNTs with tubulin. Our results suggest that CCT4 drives the formation of microtubule‐containing tunneling nanotubes.

## Linked entities

- **Genes:** CCT4 (chaperonin containing TCP1 subunit 4) [NCBI Gene 10575]
- **Proteins:** CCT4 (chaperonin containing TCP1 subunit 4), gammaTub23C (gamma-Tubulin at 23C), ACTIN (hypothetical protein)

## Full-text entities

- **Genes:** MARVELD2 (MARVEL domain containing 2) [NCBI Gene 153562] {aka DFNB49, MARVD2, MRVLDC2, Tric}, CCT4 (chaperonin containing TCP1 subunit 4) [NCBI Gene 10575] {aka CCT-DELTA, Cctd, SRB}

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12793717/full.md

## References

35 references — full list in the complete paper: https://tomesphere.com/paper/PMC12793717/full.md

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Source: https://tomesphere.com/paper/PMC12793717