Sandbox Reserved 818: Difference between revisions

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<ref name="Schmidt MA (1997)">
<ref name="Schmidt MA (1997)">
El Baya, A., Linnemann, R., von Olleschik-Elbheim, L., Robenek, H., & Schmidt, M. A. (1997). Endocytosis and retrograde transport of pertussis toxin to the Golgi complex as a prerequisite for cellular intoxication. European journal of cell biology, 73(1), 40.
El Baya, A., Linnemann, R., von Olleschik-Elbheim, L., Robenek, H., & Schmidt, M. A. (1997). Endocytosis and retrograde transport of pertussis toxin to the Golgi complex as a prerequisite for cellular intoxication. European journal of cell biology, 73(1), 40.
</ref>.[75,76].
</ref>
<ref name="Xu95">
Xu, Y., & Barbieri, J. T. (1995). Pertussis toxin-mediated ADP-ribosylation of target proteins in Chinese hamster ovary cells involves a vesicle trafficking mechanism. Infection and immunity, 63(3), 825-832.
</ref>.


Electron microscopy studies have shown that PTX enters the cells via coated pits  
Electron microscopy studies have shown that PTX enters the cells via coated pits  
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But for now, PTX does not contain a clearly identified translocation domain in the B moiety.
But for now, PTX does not contain a clearly identified translocation domain in the B moiety.


S1 is able to bind to phospholipids bilayers [78], suggesting that it may directly interact with the target cell membranes and mediate its translocation, and also that the B oligomer is not essential for this step. Results obtained from cell transfection experiments support this hypothesis [80,81].
S1 is able to bind to phospholipids bilayers
<ref name="Carbonetti08">
Plaut, R. D., & Carbonetti, N. H. (2008). Retrograde transport of pertussis toxin in the mammalian cell. Cellular microbiology, 10(5), 1130-1139.
</ref>
, suggesting that it may directly interact with the target cell membranes and mediate its translocation, and also that the B oligomer is not essential for this step. Results obtained from cell transfection experiments support this hypothesis  
<ref name="Carbonetti01">
Castro, M. G., McNamara, U., & Carbonetti, N. H. (2001). Expression, activity and cytotoxicity of pertussis toxin S1 subunit in transfected mammalian cells. Cellular microbiology, 3(1), 45-54.
</ref>
<ref name="Locht00">
Veithen, A., Raze, D., & Locht, C. (2000). Intracellular trafficking and membrane translocation of pertussis toxin into host cells. International journal of medical microbiology, 290(4), 409-413.
</ref>.


Binding of ATP to PTX [82] destabilizes the S1–B oligomer interactions and results in the release of S1 from the holotoxin [83]. This was proposed to occur in the endoplasmic reticulum, as it contain ATP and [http://en.wikipedia.org/wiki/Protein_disulfide-isomerase disulfide isomerases], that may reduce the intramolecular disulphide bonds of S1, therefore help to release the subunit from the holotoxin [85,86].
Binding of ATP to PTX  
<ref name="Read96">
Hazes, B., Boodhoo, A., Cockle, S. A., & Read, R. J. (1996). Crystal structure of the pertussis toxin–ATP Complex: A molecular sensor. Journal of molecular biology, 258(4), 661-671.
</ref>
destabilizes the S1–B oligomer interactions and results in the release of S1 from the holotoxin
<ref name="Read97">
Hazes, B., & Read, R. J. (1997). Accumulating evidence suggests that several AB-toxins subvert the endoplasmic reticulum-associated protein degradation pathway to enter target cells. Biochemistry, 36(37), 11051-11054.
</ref>.
This was proposed to occur in the endoplasmic reticulum, as it contain ATP and [http://en.wikipedia.org/wiki/Protein_disulfide-isomerase disulfide isomerases], that may reduce the intramolecular disulphide bonds of S1, therefore help to release the subunit from the holotoxin
<ref name="Hewlett83">
Moss, J., Stanley, S. J., Burns, D. L., Hsia, J. A., Yost, D. A., Myers, G. A., & Hewlett, E. L. (1983). Activation by thiol of the latent NAD glycohydrolase and ADP-ribosyltransferase activities of Bordetella pertussis toxin (islet-activating protein). Journal of Biological Chemistry, 258(19), 11879-11882.
</ref>.


These observations imply that the holotoxin traffics via the endosomal pathway and Golgi apparatus to the endoplasmic reticulum, where it meet ATP and disulphide isomerase, leading to the release of the S1 subunit. S1 then translocate directly through the endoplasmic reticulum membrane into the cytosol (Fig ?)
These observations imply that the holotoxin traffics via the endosomal pathway and Golgi apparatus to the endoplasmic reticulum, where it meet ATP and disulphide isomerase, leading to the release of the S1 subunit. S1 then translocate directly through the endoplasmic reticulum membrane into the cytosol (Fig ?)
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