Cargando…

Insights on the trafficking and retro-translocation of glycosphingolipid-binding bacterial toxins

Some bacterial toxins and viruses have evolved the capacity to bind mammalian glycosphingolipids to gain access to the cell interior, where they can co-opt the endogenous mechanisms of cellular trafficking and protein translocation machinery to cause toxicity. Cholera toxin (CT) is one of the best-s...

Descripción completa

Detalles Bibliográficos
Autores principales: Cho, Jin A., Chinnapen, Daniel J.-F., Aamar, Emil, te Welscher, Yvonne M., Lencer, Wayne I., Massol, Ramiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3417474/
https://www.ncbi.nlm.nih.gov/pubmed/22919642
http://dx.doi.org/10.3389/fcimb.2012.00051
_version_ 1782240501880061952
author Cho, Jin A.
Chinnapen, Daniel J.-F.
Aamar, Emil
te Welscher, Yvonne M.
Lencer, Wayne I.
Massol, Ramiro
author_facet Cho, Jin A.
Chinnapen, Daniel J.-F.
Aamar, Emil
te Welscher, Yvonne M.
Lencer, Wayne I.
Massol, Ramiro
author_sort Cho, Jin A.
collection PubMed
description Some bacterial toxins and viruses have evolved the capacity to bind mammalian glycosphingolipids to gain access to the cell interior, where they can co-opt the endogenous mechanisms of cellular trafficking and protein translocation machinery to cause toxicity. Cholera toxin (CT) is one of the best-studied examples, and is the virulence factor responsible for massive secretory diarrhea seen in cholera. CT enters host cells by binding to monosialotetrahexosylganglioside (GM1 gangliosides) at the plasma membrane where it is transported retrograde through the trans-Golgi network (TGN) into the endoplasmic reticulum (ER). In the ER, a portion of CT, the CT-A1 polypeptide, is unfolded and then “retro-translocated” to the cytosol by hijacking components of the ER associated degradation pathway (ERAD) for misfolded proteins. CT-A1 rapidly refolds in the cytosol, thus avoiding degradation by the proteasome and inducing toxicity. Here, we highlight recent advances in our understanding of how the bacterial AB(5) toxins induce disease. We highlight the molecular mechanisms by which these toxins use glycosphingolipid to traffic within cells, with special attention to how the cell senses and sorts the lipid receptors. We also discuss several new studies that address the mechanisms of toxin unfolding in the ER and the mechanisms of CT A1-chain retro-translocation to the cytosol.
format Online
Article
Text
id pubmed-3417474
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-34174742012-08-23 Insights on the trafficking and retro-translocation of glycosphingolipid-binding bacterial toxins Cho, Jin A. Chinnapen, Daniel J.-F. Aamar, Emil te Welscher, Yvonne M. Lencer, Wayne I. Massol, Ramiro Front Cell Infect Microbiol Microbiology Some bacterial toxins and viruses have evolved the capacity to bind mammalian glycosphingolipids to gain access to the cell interior, where they can co-opt the endogenous mechanisms of cellular trafficking and protein translocation machinery to cause toxicity. Cholera toxin (CT) is one of the best-studied examples, and is the virulence factor responsible for massive secretory diarrhea seen in cholera. CT enters host cells by binding to monosialotetrahexosylganglioside (GM1 gangliosides) at the plasma membrane where it is transported retrograde through the trans-Golgi network (TGN) into the endoplasmic reticulum (ER). In the ER, a portion of CT, the CT-A1 polypeptide, is unfolded and then “retro-translocated” to the cytosol by hijacking components of the ER associated degradation pathway (ERAD) for misfolded proteins. CT-A1 rapidly refolds in the cytosol, thus avoiding degradation by the proteasome and inducing toxicity. Here, we highlight recent advances in our understanding of how the bacterial AB(5) toxins induce disease. We highlight the molecular mechanisms by which these toxins use glycosphingolipid to traffic within cells, with special attention to how the cell senses and sorts the lipid receptors. We also discuss several new studies that address the mechanisms of toxin unfolding in the ER and the mechanisms of CT A1-chain retro-translocation to the cytosol. Frontiers Media S.A. 2012-04-11 /pmc/articles/PMC3417474/ /pubmed/22919642 http://dx.doi.org/10.3389/fcimb.2012.00051 Text en Copyright © 2012 Cho, Chinnapen, Aamar, te Welscher, Lencer and Massol. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
spellingShingle Microbiology
Cho, Jin A.
Chinnapen, Daniel J.-F.
Aamar, Emil
te Welscher, Yvonne M.
Lencer, Wayne I.
Massol, Ramiro
Insights on the trafficking and retro-translocation of glycosphingolipid-binding bacterial toxins
title Insights on the trafficking and retro-translocation of glycosphingolipid-binding bacterial toxins
title_full Insights on the trafficking and retro-translocation of glycosphingolipid-binding bacterial toxins
title_fullStr Insights on the trafficking and retro-translocation of glycosphingolipid-binding bacterial toxins
title_full_unstemmed Insights on the trafficking and retro-translocation of glycosphingolipid-binding bacterial toxins
title_short Insights on the trafficking and retro-translocation of glycosphingolipid-binding bacterial toxins
title_sort insights on the trafficking and retro-translocation of glycosphingolipid-binding bacterial toxins
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3417474/
https://www.ncbi.nlm.nih.gov/pubmed/22919642
http://dx.doi.org/10.3389/fcimb.2012.00051
work_keys_str_mv AT chojina insightsonthetraffickingandretrotranslocationofglycosphingolipidbindingbacterialtoxins
AT chinnapendanieljf insightsonthetraffickingandretrotranslocationofglycosphingolipidbindingbacterialtoxins
AT aamaremil insightsonthetraffickingandretrotranslocationofglycosphingolipidbindingbacterialtoxins
AT tewelscheryvonnem insightsonthetraffickingandretrotranslocationofglycosphingolipidbindingbacterialtoxins
AT lencerwaynei insightsonthetraffickingandretrotranslocationofglycosphingolipidbindingbacterialtoxins
AT massolramiro insightsonthetraffickingandretrotranslocationofglycosphingolipidbindingbacterialtoxins