Ricin Trafficking in Cells
The heterodimeric plant toxin ricin binds exposed galactosyls at the cell surface of target mammalian cells, and, following endocytosis, is transported in vesicular carriers to the endoplasmic reticulum (ER). Subsequently, the cell-binding B chain (RTB) and the catalytic A chain (RTA) are separated...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-01-01
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| Series: | Toxins |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2072-6651/7/1/49 |
| _version_ | 1798039364663508992 |
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| author | Robert A. Spooner J. Michael Lord |
| author_facet | Robert A. Spooner J. Michael Lord |
| author_sort | Robert A. Spooner |
| collection | DOAJ |
| description | The heterodimeric plant toxin ricin binds exposed galactosyls at the cell surface of target mammalian cells, and, following endocytosis, is transported in vesicular carriers to the endoplasmic reticulum (ER). Subsequently, the cell-binding B chain (RTB) and the catalytic A chain (RTA) are separated reductively, RTA embeds in the ER membrane and then retrotranslocates (or dislocates) across this membrane. The protein conducting channels used by RTA are usually regarded as part of the ER-associated protein degradation system (ERAD) that removes misfolded proteins from the ER for destruction by the cytosolic proteasomes. However, unlike ERAD substrates, cytosolic RTA avoids destruction and folds into a catalytic conformation that inactivates its target ribosomes. Protein synthesis ceases, and subsequently the cells die apoptotically. This raises questions about how this protein avoids the pathways that are normally sanctioned for ER-dislocating substrates. In this review we focus on the molecular events that occur with non-tagged ricin and its isolated subunits at the ER–cytosol interface. This focus reveals that intra-membrane interactions of RTA may control its fate, an area that warrants further investigation. |
| first_indexed | 2024-04-11T21:52:52Z |
| format | Article |
| id | doaj.art-153aa7b345bd42a48200f4a368297306 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T21:52:52Z |
| publishDate | 2015-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-153aa7b345bd42a48200f4a3682973062022-12-22T04:01:11ZengMDPI AGToxins2072-66512015-01-0171496510.3390/toxins7010049toxins7010049Ricin Trafficking in CellsRobert A. Spooner0J. Michael Lord1School of Life Sciences, University of Warwick, Coventry CV4 7AL, UKSchool of Life Sciences, University of Warwick, Coventry CV4 7AL, UKThe heterodimeric plant toxin ricin binds exposed galactosyls at the cell surface of target mammalian cells, and, following endocytosis, is transported in vesicular carriers to the endoplasmic reticulum (ER). Subsequently, the cell-binding B chain (RTB) and the catalytic A chain (RTA) are separated reductively, RTA embeds in the ER membrane and then retrotranslocates (or dislocates) across this membrane. The protein conducting channels used by RTA are usually regarded as part of the ER-associated protein degradation system (ERAD) that removes misfolded proteins from the ER for destruction by the cytosolic proteasomes. However, unlike ERAD substrates, cytosolic RTA avoids destruction and folds into a catalytic conformation that inactivates its target ribosomes. Protein synthesis ceases, and subsequently the cells die apoptotically. This raises questions about how this protein avoids the pathways that are normally sanctioned for ER-dislocating substrates. In this review we focus on the molecular events that occur with non-tagged ricin and its isolated subunits at the ER–cytosol interface. This focus reveals that intra-membrane interactions of RTA may control its fate, an area that warrants further investigation.http://www.mdpi.com/2072-6651/7/1/49ricinER-cytosol retrotranslocationp24 proteinsERP2HRD1proteasomeRPTchaperone |
| spellingShingle | Robert A. Spooner J. Michael Lord Ricin Trafficking in Cells Toxins ricin ER-cytosol retrotranslocation p24 proteins ERP2 HRD1 proteasome RPT chaperone |
| title | Ricin Trafficking in Cells |
| title_full | Ricin Trafficking in Cells |
| title_fullStr | Ricin Trafficking in Cells |
| title_full_unstemmed | Ricin Trafficking in Cells |
| title_short | Ricin Trafficking in Cells |
| title_sort | ricin trafficking in cells |
| topic | ricin ER-cytosol retrotranslocation p24 proteins ERP2 HRD1 proteasome RPT chaperone |
| url | http://www.mdpi.com/2072-6651/7/1/49 |
| work_keys_str_mv | AT robertaspooner ricintraffickingincells AT jmichaellord ricintraffickingincells |