CCT4 promotes tunneling nanotube formation

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 statement 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.