Revealing the structure and organization of intercellular tunneling nanotubes (TNTs) by STORM imaging

Huang, Lilin; Zhang, Jiao; Wu, Zekai; Zhou, Liangliang; Yu, Bin; Jing, Yingying; Lin, Danying; Qu, Junle

doi:10.1039/d2na00415a

Cited by 8 publications

(10 citation statements)

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“…TNTs are thin, delicate structures that are difficult to isolate and visualize. Nevertheless, advanced imaging techniques, live-cell imaging, and electron microscopy are routinely used to visualize TNTs, but these techniques require specialized equipment and expertise [34,42]. In addition, the fragility of TNTs makes them difficult to manipulate and study in vitro, as they are easily damaged during cell isolation and culture.…”

Section: Challenges Involved In Researching Tnts In the Brainmentioning

confidence: 99%

“…Despite the growing recognition of TNTs' significance in the nervous system and brain, there are technical challenges associated with their identification and visualization in vivo and within complex brain tissues. However, new developments in imaging methods, including super-resolution microscopy, along with the application of organoid models, have offered insightful knowledge on TNT biology in a more physiologically relevant setting [31][32][33][34]. These advancements pave the way for further exploration of TNT function and dynamics within complex neural networks.…”

Section: Introductionmentioning

confidence: 99%

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Tunneling Nanotube: An Enticing Cell–Cell Communication in the Nervous System

Dagar,

Subramaniam

2023

Biology

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The field of neuroscience is rapidly progressing, continuously uncovering new insights and discoveries. Among the areas that have shown immense potential in research, tunneling nanotubes (TNTs) have emerged as a promising subject of study. These minute structures act as conduits for the transfer of cellular materials between cells, representing a mechanism of communication that holds great significance. In particular, the interplay facilitated by TNTs among various cell types within the brain, including neurons, astrocytes, oligodendrocytes, glial cells, and microglia, can be essential for the normal development and optimal functioning of this complex organ. The involvement of TNTs in neurodegenerative disorders, such as Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease, has attracted significant attention. These disorders are characterized by the progressive degeneration of neurons and the subsequent decline in brain function. Studies have predicted that TNTs likely play critical roles in the propagation and spread of pathological factors, contributing to the advancement of these diseases. Thus, there is a growing interest in understanding the precise functions and mechanisms of TNTs within the nervous system. This review article, based on our recent work on Rhes-mediated TNTs, aims to explore the functions of TNTs within the brain and investigate their implications for neurodegenerative diseases. Using the knowledge gained from studying TNTs could offer novel opportunities for designing targeted treatments that can stop the progression of neurodegenerative disorders.

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Section: Challenges Involved In Researching Tnts In the Brainmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tunneling Nanotube: An Enticing Cell–Cell Communication in the Nervous System

Dagar,

Subramaniam

2023

Biology

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“…Both terminals of TNTs are open to the cytoplasm, allowing matter exchange between adjacent cells (Taiarol et al., 2021 ). TNTs are further divided into two categories: ‘thin TNT’ and ‘thick TNT.’ In thin TNT, the diameter varies between 20 and 700 nm, and in thick TNT, the diameter > 700 nm, and its length can reach several hundreds of micrometers (Huang et al., 2022 ). ‘Thick’ TNTs are composed of both actin and tubulin filaments, while ‘thin’ TNTs only contain actin filaments.…”

Section: Direct Transfer To Facilitate the Drug Deliverymentioning

confidence: 99%

The direct transfer approach for transcellular drug delivery

Wang,

Shen,

Xiang

et al. 2023

Drug Delivery

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A promising paradigm for drug administration that has garnered increasing attention in recent years is the direct transfer (DT) of nanoparticles for transcellular drug delivery. DT requires direct cell-cell contact and facilitates unidirectional and bidirectional matter exchange between neighboring cells. Consequently, DT enables fast and deep penetration of drugs into the targeted tissues. This comprehensive review discusses the direct transfer concept, which can be delineated into the following three distinct modalities: membrane contact-direct transfer, gap junction-mediated direct transfer (GJ-DT), and tunneling nanotubes-mediated direct transfer (TNTs-DT). Further, the intercellular structures for each modality of direct transfer and their respective merits and demerits are summarized. The review also discusses the recent progress on the drugs or drug delivery systems that could activate DT.

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“…While different mechanisms for the transcellular transfer of mitochondria have been identified, including extracellular vesicles and gap junction channels [ 105 ], TNTs represent unique actin-rich structures that provide cytoplasmatic continuity between cells, enabling the bidirectional transport of cargoes. TNTs are membrane protrusions linking two or more cells and, as such, they have been described in multiple cell types [ 106 ]. They form transient cytoplasmic bridges containing a skeleton mainly composed of F-actin, microtubules or both.…”

Section: Specialized Cytoskeleton Structures Allow Mitochondria To Cr...mentioning

confidence: 99%

Highly Specialized Mechanisms for Mitochondrial Transport in Neurons: From Intracellular Mobility to Intercellular Transfer of Mitochondria

Zaninello

Bean

2023

Biomolecules

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The highly specialized structure and function of neurons depend on a sophisticated organization of the cytoskeleton, which supports a similarly sophisticated system to traffic organelles and cargo vesicles. Mitochondria sustain crucial functions by providing energy and buffering calcium where it is needed. Accordingly, the distribution of mitochondria is not even in neurons and is regulated by a dynamic balance between active transport and stable docking events. This system is finely tuned to respond to changes in environmental conditions and neuronal activity. In this review, we summarize the mechanisms by which mitochondria are selectively transported in different compartments, taking into account the structure of the cytoskeleton, the molecular motors and the metabolism of neurons. Remarkably, the motor proteins driving the mitochondrial transport in axons have been shown to also mediate their transfer between cells. This so-named intercellular transport of mitochondria is opening new exciting perspectives in the treatment of multiple diseases.

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Revealing the structure and organization of intercellular tunneling nanotubes (TNTs) by STORM imaging

Abstract: Tunneling nanotubes (TNTs) are nanoscale, actin-rich, transient intercellular tubes for cell-to-cell communication, which transport various cargoes between distant cells. The structural complexity and spatial organization of the involved components of...

Cited by 8 publications

References 45 publications

Tunneling Nanotube: An Enticing Cell–Cell Communication in the Nervous System

Tunneling Nanotube: An Enticing Cell–Cell Communication in the Nervous System

The direct transfer approach for transcellular drug delivery

Highly Specialized Mechanisms for Mitochondrial Transport in Neurons: From Intracellular Mobility to Intercellular Transfer of Mitochondria

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