User:Smbiophysics/Tunneling nanotube

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Article Draft[edit]

Lead[edit]

FINAL THINGS: Add part about Arp2/3 and WASP/WAVE? Or just about Arp2/3 both inhibiting and promoting TNT

Remove link from "BnL-FGF" gradient. FGF (fibroblast growth factor) is protein whose homolog in drosophila is produced by gene branchless (bnl). Add link to FGF gradient, and bnl is a gene in drosophila that produces a FGF homolog

"Streamers" could use a description to describe what it is as a nanotube structure. This section should be moved to TNT like structures, as it cannot be inferred that TNT's are inhibited by actin depolymerization.

Portland Press article for talking about Arp2/3's inhibition actually promoted more cells connected via TNT's, but less TNT's overall

Portland Press for WASP and WAVE interaction with polymerizing actin

Myopodia in article has incorrect link to pseudopods. There is no link to Myopodia so I will need to remove it.

Under Applications Section:

Tunneling nanotubes have the potential to be involved in the field of nanomedicine, as they have shown the ability to inter-cellularly transfer such treatments.

Image:

Tunelling[sic] nanotube on Wikimedia Commons add to history section

3D live-cell microscopy of immunofluorescent rat PC12 cells demonstrating tunneling nanotubes. From one of the first published papers to describe the phenomenon in 2004.

-Clarify that viruses can induce TNT formation in cells, they do not form their own (Kade feedback)

-Include video on microtubule presence

-Include part about active diffusion

Edits:

Clear up image description:

A High resolution 3D live-cell fluorescence image of a tunneling nanotube (TNT) (white arrow) connecting two primary mesothelial cells. Scale bar: 20 μm.

B Depiction of a TNT (black arrow) between two cells with scanning electron microscopy. Scale bar: 10 μm.

C Fluorescently labeled F-actin (white arrow) present in TNTs between individual HPMCs. Scale bar: 20 μm.

D Scanning electron microscope image of a potential TNT precursor (black arrowhead). Insert shows a fluorescence microscopic image of filopodia-like protrusions (white arrowhead) approaching a neighboring cell. Scale bar: 2 μm.

A tunneling nanotube (TNT) or membrane nanotube is a term that has been applied to cytoskeletal protrusions that extend from the plasma membrane which enable different animal cells to connect over long distances, sometimes over 100 μm between certain types of cells.

Tunneling nanotubes that are less than 0.7 micrometers in diameter, have an actin structure and carry portions of plasma membrane between cells in both directions. Larger TNTs (>0.7 μm), contain an actin structure with microtubules and/or intermediate filaments, and can carry components of the cytoplasm such as vesicles and organelles between cells, including whole mitochondria. [1](reference for all three in a TNT)

The diameter of TNTs ranges from 0.05 μm to 1.5 μm and they can reach lengths of several cell diameters.[2] There have been two types of observed TNTs: open ended and closed ended. Open ended TNTs are effectively hollow and connect the cytoplasm of two cells. Closed ended TNTs do not have continuous cytoplasm as there is a gap junction cap that only allows small molecules and ions to flow between cells. [3]

These structures have shown involvement in cell-to-cell communication, transfer of nucleic acids such as mRNA and miRNA between cells in culture or in a tissue, and the spread of pathogens or toxins such as HIV and prions.

and several proteins have been implicated in their formation or inhibition, primarily those that interact with Arp2/3.[4]

More recently, a Science article published in 2004 described structures that connected PC12 cells together, as well as other types of cell cultures. This study coined the term "tunneling nanotubes" and also showed that nanotube formation between cells is correlated with both membrane and organelle transfer.[5] (reference already used in their paper)

The other mechanism occurs when two previously connected cells move away from one another, and TNTs remain as bridges between the two cells.

Phosphatidylserine exposure has demonstrated the ability to guide TNT formation from mesenchymal stem cells (MSCs) to a population of injured cells. Additionally, the protein S100A4 and its receptor have been shown to guide the direction of TNT growth, as p53 activates caspase 3 to cleave S100A4 in the initiating cell, thereby generating a gradient in which the target cell has higher amounts of the protein. These findings suggests that chemotactic gradients may be involved in TNT induction.

TNTs have many components, but their main inhibitors work by blocking or limiting actin formation. TNT-like structures called streamers, which are thinner versions of cytonemes, did not form when cultured with [6]

Inhibiting Arp2/3 directly resulted in different effects depending on cell type. In human eye cells and macrophages, blocking Arp2/3 led to a decrease in TNT formation. However, such inhibition in neuronal cells resulted in an increase in the amount of cells connected via TNTs, while lowering the total amount of TNTs connecting cells. [7]

Change subheading to "Roles in intercellular transfer" (while I won't be adding a lot, this is a general section that can be added to easier)

Add Mitochondrial Transfer as a subsubheading

Add Virus Transfer

Add Nanomedicine transfer

Interestingly, A recent study in Nature Nanotechnology has reported that cancer cells can hijack the mitochondria from immune cells via physical tunneling nanotubes

Tunneling nanotubes have been shown to propagate action potentials via their extensions of endoplasmic reticulum that propagate Ca2+ influx. [8]

Many viruses can transfer their proteins to TNT-connected cells. Certain types, such as influenza, have even been found to transfer their genome via TNTs.[9] Since this discovery, over two dozen types of viruses were found to transfer through and/or modulate TNT.

Tunneling nanotubes have the potential to be involved in the field of nanomedicine, as they have shown the ability to transfer such treatments between cells. Future applications look to either inhibit TNTs to prevent nanomedicine toxicity from reaching neighboring cells, or to promote TNT formation to increase positive effects of the medicine.

While TNT-like structures are all cytoskeletal cellular protrusions, their fundamental difference with TNTs is in the connection between two cells. TNT-like structures do not share intracellular contents such as ions or small molecules–a feature that is present in both open ended and closed ended TNTs. [3]

(MOVE) Cytonemes, however, do not always connect the membrane two cells and can act solely as environmental sensor. The formation of cytonemes towards a FGF homolog gradient has been observed, suggesting that chemotactic controls may also induce the formation of TNT-like structures.

Add image about cancer cells using tunneling nanotubes

Malignant cancer cells can connect via tunneling nanotubes.
EB3, a protein that binds to the positive end of polymerizing microtubules, found in tunneling nanotubes. EB3 labeled with mCherry.

Article body[edit]

References[edit]

1. Opportunities and Challenges in Tunneling Nanotubes Research: How Far from Clinical Application?[10]

2. Tunneling Nanotubes: A New Target for Nanomedicine?[11] USED for nanomedicine

3. Tunneling nanotubes and related structures: molecular mechanisms of formation and function[12] (Review article) USED for ARP2/3 inhibition/promotion

4. Extracellular Vesicles, Tunneling Nanotubes, and Cellular Interplay: Synergies and Missing Links[13]

5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572865/ for microtubule video Transfer of mitochondria via tunneling nanotubes rescues apoptotic PC12 cells

6. https://pubs-acs-org.byu.idm.oclc.org/doi/10.1021/nn303729r for 1500 nm diameter USED

7. https://journals-aai-org.byu.idm.oclc.org/jimmunol/article/177/12/8476/73972/Structurally-Distinct-Membrane-Nanotubes-between for intermediate filaments USED

8. https://www-nature-com.byu.idm.oclc.org/articles/s41598-017-08950-7 for WASP and WAVE2, etc. USED for ARP 2/3

9. https://www.sciencedirect.com/science/article/pii/S0955067421000375 USED for closed ended nanotubes having gap junctions

10. https://doi.org/10.1016/j.bpj.2011.03.007 USED for calcium propagation.

11. 10.1038/srep40360 USED for virus spreading

12. 10.4161/cib.27934 for streamers definition

Shoot for 7 references added?



-Image?

  1. ^ Resnik, Nataša; Erman, Andreja; Veranič, Peter; Kreft, Mateja Erdani (2019-08-08). "Triple labelling of actin filaments, intermediate filaments and microtubules for broad application in cell biology: uncovering the cytoskeletal composition in tunneling nanotubes". Histochemistry and Cell Biology. 152 (4): 311–317. doi:10.1007/s00418-019-01806-3. ISSN 0948-6143.
  2. ^ Wang, Zhi-Gang; Liu, Shu-Lin; Tian, Zhi-Quan; Zhang, Zhi-Ling; Tang, Hong-Wu; Pang, Dai-Wen (2012-11-01). "Myosin-Driven Intercellular Transportation of Wheat Germ Agglutinin Mediated by Membrane Nanotubes between Human Lung Cancer Cells". ACS Nano. 6 (11): 10033–10041. doi:10.1021/nn303729r. ISSN 1936-0851.
  3. ^ a b Zurzolo, Chiara (2021-08-01). "Tunneling nanotubes: Reshaping connectivity". Current Opinion in Cell Biology. Membrane Trafficking. 71: 139–147. doi:10.1016/j.ceb.2021.03.003. ISSN 0955-0674.
  4. ^ Hanna, Samer J.; McCoy-Simandle, Kessler; Miskolci, Veronika; Guo, Peng; Cammer, Michael; Hodgson, Louis; Cox, Dianne (2017-08-17). "The Role of Rho-GTPases and actin polymerization during Macrophage Tunneling Nanotube Biogenesis". Scientific Reports. 7 (1). doi:10.1038/s41598-017-08950-7. ISSN 2045-2322. PMC 5561213. PMID 28819224.{{cite journal}}: CS1 maint: PMC format (link)
  5. ^ Rustom, Amin; Saffrich, Rainer; Markovic, Ivanka; Walther, Paul; Gerdes, Hans-Hermann (2004-02-13). "Nanotubular Highways for Intercellular Organelle Transport". Science. 303 (5660): 1007–1010. doi:10.1126/science.1093133. ISSN 0036-8075.
  6. ^ Austefjord, Magnus Wiger; Gerdes, Hans-Hermann; Wang, Xiang (2014-01-30). "Tunneling nanotubes: Diversity in morphology and structure". Communicative & Integrative Biology. 7 (1): e27934. doi:10.4161/cib.27934. ISSN 1942-0889. PMC 3995728. PMID 24778759.{{cite journal}}: CS1 maint: PMC format (link)
  7. ^ Dagar, Sunayana; Pathak, Diksha; Oza, Harsh V.; Mylavarapu, Sivaram V. S. (2021-11-23). "Tunneling nanotubes and related structures: molecular mechanisms of formation and function". Biochemical Journal. 478 (22): 3977–3998. doi:10.1042/bcj20210077. ISSN 0264-6021.
  8. ^ Smith, Ian; Shuai, Jianwei; Parker, Ian (2011-04-20). "Active Generation and Propagation of Ca2+ Signals within Tunneling Membrane Nanotubes". Biophysical Journal. 100 (8): L37–L39. doi:10.1016/j.bpj.2011.03.007. ISSN 0006-3495. PMC 3077701. PMID 21504718.{{cite journal}}: CS1 maint: PMC format (link)
  9. ^ Kumar, Amrita; Kim, Jin Hyang; Ranjan, Priya; Metcalfe, Maureen G.; Cao, Weiping; Mishina, Margarita; Gangappa, Shivaprakash; Guo, Zhu; Boyden, Edward S.; Zaki, Sherif; York, Ian; García-Sastre, Adolfo; Shaw, Michael; Sambhara, Suryaprakash (2017-01-06). "Influenza virus exploits tunneling nanotubes for cell-to-cell spread". Scientific Reports. 7 (1). doi:10.1038/srep40360. ISSN 2045-2322. PMC 5216422. PMID 28059146.{{cite journal}}: CS1 maint: PMC format (link)
  10. ^ Han, Xiaoning (February 25, 2021). "Opportunities and Challenges in Tunneling Nanotubes Research: How Far from Clinical Application?". National Library of Medicine. International Journal of Molecular Sciences.
  11. ^ Putz, Mihai (February 17, 2022). "Tunneling Nanotubes: A New Target for Nanomedicine?". National Library of Medicine. International Journal of Molecular Sciences. PMID 35216348.
  12. ^ Dagar, Sunayana; Pathak, Diksha; Oza, Harsh V.; Mylavarapu, Sivaram V. S. (2021-11-26). "Tunneling nanotubes and related structures: molecular mechanisms of formation and function". The Biochemical Journal. 478 (22): 3977–3998. doi:10.1042/BCJ20210077. ISSN 1470-8728. PMID 34813650.
  13. ^ Nawaz, Muhammad; Fatima, Farah (2017). "Extracellular Vesicles, Tunneling Nanotubes, and Cellular Interplay: Synergies and Missing Links". Frontiers in Molecular Biosciences. 4. doi:10.3389/fmolb.2017.00050/full. ISSN 2296-889X.{{cite journal}}: CS1 maint: unflagged free DOI (link)