Formation of cellular close-ended tunneling nanotubes through mechanical deformation

Chang, Minhyeok; Lee, O-chul; Bu, Gayun; Oh, Jaeho; Yunn, Na-Oh; Ryu, Sung Ho; Kwon, Hyung-Bae; Kolomeisky, Anatoly B.; Shim, Sang‐Hee; Doh, Junsang; Lee, Jong–Bong

doi:10.1126/sciadv.abj3995

Cited by 24 publications

(29 citation statements)

References 40 publications

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“…Furthermore, we observed that cells forming TNTs use other pre-existing protrusions as guides to grow (Movie S7 &8), the lack of N-Cadherin would therefore cause the disappearance of these guides and therefore these iTNTs would have no reference for growth/retraction. Our data are supported by recent findings showing that double filopodial bridges (DFB, that the authors consider as precursors of close-ended TNTs in HeLa cells), were dissociated resulting into separation of paired cells by downregulating N-Cadherin (or inhibiting its function with EGTA) (38). In the same study, the authors show N-Cadherin decorating the whole DFB/TNT-like structure and preferentially enriched in the areas of contact with opposite cells.…”

Section: Discussionsupporting

confidence: 90%

N-Cadherin and α-catenin regulate formation of functional tunneling nanotubes

Pepe

Manzano

Sartori-Rupp

et al. 2023

Preprint

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Cell-to-cell communication it is a fundamental mechanism by which unicellular and multicellular organisms maintain relevant functions as development or homeostasis. Tunneling nanotubes (TNTs) are a type of contact-mediated cell-to-cell communication defined by being membranous structures based on actin that allow the exchange of different cellular material. TNTs have been shown to have unique structural features compared with other cellular protrusions and to contain the cell adhesion molecule N-Cadherin. Here, we investigated the possible role of N-Cadherin and of its primary linker to the actin cytoskeleton, alpha-Catenin in regulating the formation and transfer function of TNTs. Our data indicate that N-Cadherin through its downstream effector alpha-Catenin is a major regulator of TNT formation, ultrastructure, as well as of their ability to transfer material to other cells.

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Section: Discussionsupporting

confidence: 90%

N-Cadherin and α-catenin regulate formation of functional tunneling nanotubes

Pepe

Manzano

Sartori-Rupp

et al. 2023

Preprint

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“…The cytoskeleton of TNTs in HEK293 cells is composed of F-actin without microtubules and vimentin ( Supplementary Figure S3A ). It has been shown that cadherin adhesion molecules are present at the tip of TNTs or between thin TNTs ( Jansens et al, 2017 ; Sartori-Rupp et al, 2019 ; Chang et al, 2022 ). Here, we show that HEK293 cells expressed N-cadherin but not E-cadherin at cellular junctions ( Supplementary Figure S3B ).…”

Section: Resultsmentioning

confidence: 99%

“…It is close to the lateral force (approx. 40 pN/μm) that is needed to bend TNTs between Hela cells using optical tweezers ( Chang et al, 2022 ). Moreover, both studies revealed no threshold was required for bending TNTs.…”

Section: Discussionmentioning

confidence: 99%

“…In the study exploring the molecular determinant of mechanical stability of TNTs, we found that the elongation rate of TNTs reduced greatly when actin filament polymerization was inhibited by cytoD, suggesting again that actin cytoskeleton is the main component providing tensile strength of TNTs. Cadherin has been found in both open-ended and close-ended TNTs ( Sartori-Rupp et al, 2019 ; Chang et al, 2022 ). Cadherin proteins may provide a binding force to anchor the two membranes for maintaining the connections at the tips of TNTs ( Jansens et al, 2017 ; Sartori-Rupp et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

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Mechanical properties of tunneling nanotube and its mechanical stability in human embryonic kidney cells

Han

Deng

et al. 2022

Front. Cell Dev. Biol.

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Tunneling nanotubes (TNTs) are thin membrane tubular structures that interconnect physically separated cells. Growing evidence indicates that TNTs play unique roles in various diseases by facilitating intercellular transfer of signaling and organelles, suggesting TNTs as a potential target for disease treatment. The efficiency of TNT-dependent communication is largely determined by the number of TNTs between cells. Though TNTs are physically fragile structures, the mechanical properties of TNTs and the determinants of their mechanical stability are still unclear. Here, using atomic force microscope (AFM) and microfluidic techniques, we investigated the mechanical behavior and abundance of TNTs in human embryonic kidney (HEK293) cells upon the application of forces. AFM measurements demonstrate that TNTs are elastic structures with an apparent spring constant of 79.1 ± 16.2 pN/μm. The stiffness and membrane tension of TNTs increase by length. TNTs that elongate slower than 0.5 μm/min display higher mechanical stability, due to the growth rate of F-actin inside TNTs being limited at 0.26 μm/min. Importantly, by disturbing the cytoskeleton, membrane, or adhesion proteins of TNTs, we found that F-actin and cadherin connection dominantly determines the tensile strength and flexural strength of TNTs respectively. It may provide new clues for screening TNT-interfering drugs that alter the stability of TNTs.

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“…1177 proteins were identified in at least 9 preparations (table S1). We first observed that proteins previously described in TNTs, like actin, Myosin10 [36], ERp29 [30], or N-cadherin [2, 37] were indeed present in TNTome. Less than 100 nuclear proteins, i.e.…”

Section: Resultsmentioning

confidence: 99%

Proteomic landscape of tunneling nanotubes reveals CD9 and CD81 tetraspanins as key regulators

Manzano

Chaze

Rubinstein

et al. 2022

Preprint

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Tunneling nanotubes (TNTs) are open actin- and membrane-based channels, connecting remote cells and allowing direct transfer of cellular material (e.g. vesicles, mRNAs, protein aggregates) from cytoplasm to cytoplasm. Although they are important especially in pathological conditions (e.g., cancers, neurodegenerative diseases), their precise composition and their regulation were still poorly described. Here, using a biochemical approach allowing to separate TNTs from cell bodies and from extracellular vesicles and particles (EVPs), we obtained the full composition of TNTs compared to EVPs. We then focused to two major components of our proteomic data, the CD9 and CD81 tetraspanins, and further investigated their specific roles in TNT formation and function. We show that these two tetraspanins have distinct functions: CD9 participates in the initiation of TNTs, whereas CD81 expression is required to allow the functional transfer of vesicle in the newly formed TNTs, possibly by regulating fusion with the opposing cell.

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Formation of cellular close-ended tunneling nanotubes through mechanical deformation

Cited by 24 publications

References 40 publications

N-Cadherin and α-catenin regulate formation of functional tunneling nanotubes

N-Cadherin and α-catenin regulate formation of functional tunneling nanotubes

Mechanical properties of tunneling nanotube and its mechanical stability in human embryonic kidney cells

Proteomic landscape of tunneling nanotubes reveals CD9 and CD81 tetraspanins as key regulators

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