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Table 1 Summary of significant reports in the field of TNT biology

From: Perspective on nanochannels as cellular mediators in different disease conditions

Research

Findings

References

Discovery

Protrusion based communication which includes TNTs are ubiquitous. They were reported clearly for the first time by Rustom et al. in rat neuronal PC12 cells

[7, 44, 55]

Structural composition

Different types of TNTs have differences in the cytoskeleton and lipid composition. Thin membrane nanotubes contain only F-actin whereas thick membrane (> ~ 0.7 μm diameter) contain F-actin as well as microtubules. Presence of specific organelles in different types of TNT’s were reported. Thick membrane nanotubes contain mitochondria, late endosomes, lysosomes and intracellular vesicles unlike thin membrane nanotubes.

[24]

Characteristic properties

Radii in between 25 and 100 μm; form connections between cells; cytoskeleton proteins such as F actin and microtubules are present; help in propagation of selected molecules and vesicles between cells; sensitive to mechanical stress; formed through de novo actin driven protrusions as well as through alternative mechanisms.

[21, 44]

Function

• Significant transfer of cell surface protein and mitochondria in between cells through TNT’s was reported.

• TNTs are found in myeloid cells where they perform different functions important for their cellular communication.

• Calcium fluxes through nanotubes which has role in cellular communication.

• Role of TNTs in senescent endothelial cell rescue.

• Transport and hijacking of TNTs by prions.

[8, 9, 12, 52, 44, 57,58,59]

Role in disease progression

• HIV transmission through TNTs between T cells, Influenza virus transmission through TNTs, TNTs formation in HIV infected cells (macrophages), TNTs are also found during the progression of HSV and PRRSV infection.

• Modulation of chemo-resistance in cancer through endothelial to cancer cell mitochondrial transfer. Modulation of endothelial phenotype through cancer TNTs, Induction of TNT formation in ovarian cancer cells through hypoxia conditions, Involvement of TNTs in tumor growth, differentiation and resistance to therapies.

• Transfer of oncogenic mRNAs by TNTs; Induction of TNTs by tumor exosomes.

• TNTs in ischemic stroke recovery.

• Role of TNFα-induced protein 2 (TNFAIP2) in TNT formation

[2, 6, 10, 11, 22, 26, 27, 29, 30, 32, 39, 40, 47, 53, 60,61,62,63]