Nanotubes facilitate intercellular signaling in eukaryotic and prokaryotic cells

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Overview


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Cells encourage diversity by using several different molecular signaling mechanisms to transfer information, nutrients, organelles, or parasites. Many of these processes require direct cellular interaction for signals to be exchanged. Prokaryotes use conjugation as a means for horizontal gene transfer from one cell to another. Eukaryotes use gap junctions to permit passage of ions and small molecules between the cytoplasm of one cell to another. Many quorum sensing eukaryotes and prokaryotes use extracellular signaling molecules to synchronize their gene expression, behavior, and population density and thus exhibit multicellular properties.[1],[2] Other single-celled or multicellular organisms (and even cancerous cells) release extracellular membrane vesicles or exosomes to shuttle microRNAs, mRNAs, DNA fragments, and proteins to a recipient cell.[3] Additionally, recent research has shown nanotubes (also called tunneling nanotubes (TNTs) or membrane nanotubes (MNTs)) to transiently form between two or more eukaryotic or prokaryotic cells (Figure 1). These nanotubular channels are cell-to-cell plasma membrane connections of varying lengths that allow for bridging cargo exchange and, in some cases, multicellular properties.

Emerging research within the past 10 years has affirmed cellular nanotubes to be involved in complex signaling processes such as viral and prion pathogenesis among eukaryotic cells and metabolic or genetic exchanges among many types of bacteria. Surprisingly, the retrovirus HIV-1 has been shown to move between T-cells, macrophages, and B-cells by use of a nanotube-delivery mechanism for viral proteins.[15],[16],[20],[22] The leukemia-causing HTLV-1 similarly spreads throughout human T-cells by a similar mechanism to HIV-1, and this mechanism allows for a powerful and rapid transmission of the virus throughout the immune system. Prions (PrPSc) that cause degenerative neural disease have been shown to take over nanotubes in bone-marrow derived dendritic cells and spread by them to neural cells, allowing for a safe intercellular route to the brain.[12] Pathogens can indeed utilize already-existing nanotubes between cells, but they have been shown in some cases to even induce nanotube formation.[22] Elucidation of these eukaryotic mechanisms could provide potential targets for drug therapy in otherwise untreatable or hard-to-treat diseases. However, transport of cytoplasmic material through nanotubes is not an activity limited only to eukaryotic cells. Both similar and diverse species of bacteria have been observed to exchange not only cytoplasmic constituents, but also genetic material in the form of plasmids.[19] Dynamic nanotubes have been witnessed between the likes of B. subtilis, E. coli, Staphylococcus aureus, and Acinetobacter baylyi.[18],[19] The new discovery of a stress-induced mutualistic nutrient exchange between distantly related species of bacteria pushes the boundaries of our definition of “unicellular” organisms and prompts us to reevaluate bacteria as a multicellular, interconnected domain of life.[18]




Structure


Include some current research in each topic, with at least one figure showing data.

Formation

Figure 2. Two general modes of nanotube formation between cells. (A) Previously adjoined cells can dislodge, forming a trailing nanotube. (B) One cell can grow a cellular protrusion and use it to make contact with another cell. [10]
<http://link.springer.com/article/10.1007%2Fs11427-013-4548-3>.


Include some current research in each topic, with at least one figure showing data.

HIV Pathogenesis

Figure 3. Detection of HIV-p24 (green staining) and actin (Texas Red-phalloidin, red staining) in macrophages containing DAPI (blue staining) through fluorescent staining. (C) Nanotubes found in HIV-infected human macrophages three days post-infection. (D-F) An enlargement of the nanotubes in the white box shown in (C). Panels (D) and (E) were merged to form panel (F), in which nanotubes containing HIV-p24 can be seen. [16]
<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701345/figure/F5/>.


Include some current research in each topic, with at least one figure showing data.

HTLV Pathogenesis


Overall paper length should be 3,000 words, with at least 3 figures.

Prion Pathogenesis

Figure 4. Nanotubular prion transfer in mice from infected ScCAD cells to non-infected CAD neuronal cells in coculture. CAD cells are depicted as red (Cherry PLAP transfection), and ScCAD cells are depicted as green (immunostaining for prions using SAF32 Ab). (C) Enlarged imaging of nanotubes carrying prions (green) from the donor ScCAD cell to the recipient CAD cell and into the cytoplasm (see arrows) <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712606/figure/F1/>.


Include some current research in each topic, with at least one figure showing data.

Prion Pathogenesis


Include some current research in each topic, with at least one figure showing data.

Genetic and cytoplasmic exchange in B. subtilis


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Metabolic mutualism between E. coli and Acinetobacter baylyi


Include some current research in each topic, with at least one figure showing data.

References

[Sample reference] Takai, K., Sugai, A., Itoh, T., and Horikoshi, K. "Palaeococcus ferrophilus gen. nov., sp. nov., a barophilic, hyperthermophilic archaeon from a deep-sea hydrothermal vent chimney". International Journal of Systematic and Evolutionary Microbiology. 2000. Volume 50. p. 489-500.

Edited by student of Joan Slonczewski for BIOL 238 Microbiology, 2009, Kenyon College.