A New Role for Clathrin Adaptor Proteins 1 and 3 in Lipoplex Trafficking
Intracellular protein trafficking through secretory and endocytic pathways depends on the function of adaptor proteins that bind motifs on cargo proteins. The adaptor proteins then recruit coat proteins such as clathrin, enabling the formation of a transport vesicle. While studying the role of the c...
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| Format: | Online |
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Public Library of Science
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950295/ |
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pubmed-3950295 |
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pubmed-39502952014-03-12 A New Role for Clathrin Adaptor Proteins 1 and 3 in Lipoplex Trafficking Alford, Justine E. Gumbs, Jade Anderson, Emma C. Research Article Intracellular protein trafficking through secretory and endocytic pathways depends on the function of adaptor proteins that bind motifs on cargo proteins. The adaptor proteins then recruit coat proteins such as clathrin, enabling the formation of a transport vesicle. While studying the role of the clathrin adaptor proteins, AP-1, AP-2 and AP-3 in viral protein trafficking, we discovered that AP-1 and AP-3 potentially have a role in successful transfection of mammalian cells with DNA-liposome complexes (lipoplexes). We showed that AP-1, -2 and -3 are not required for lipoplexes to enter cells, but that lipoplexes and/or released DNA are unable to reach the nucleus in the absence of AP-1 or AP-3, leading to minimal exogenous gene expression. In contrast, gene expression from liposome-delivered mRNA, which does not require nuclear entry, was not impaired by the absence of AP-1 or AP-3. Despite the use of lipoplexes to mediate gene delivery being so widely used in cell biology and, more recently, gene therapy, the mechanism by which lipoplexes or DNA reach the nucleus is poorly characterised. This work sheds light on the components involved in this process, and demonstrates a novel role for AP-1 and AP-3 in trafficking lipoplexes. Public Library of Science 2014-03-11 /pmc/articles/PMC3950295/ /pubmed/24618578 http://dx.doi.org/10.1371/journal.pone.0091429 Text en © 2014 Alford et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Alford, Justine E. Gumbs, Jade Anderson, Emma C. |
| spellingShingle |
Alford, Justine E. Gumbs, Jade Anderson, Emma C. A New Role for Clathrin Adaptor Proteins 1 and 3 in Lipoplex Trafficking |
| author_facet |
Alford, Justine E. Gumbs, Jade Anderson, Emma C. |
| author_sort |
Alford, Justine E. |
| title |
A New Role for Clathrin Adaptor Proteins 1 and 3 in Lipoplex Trafficking |
| title_short |
A New Role for Clathrin Adaptor Proteins 1 and 3 in Lipoplex Trafficking |
| title_full |
A New Role for Clathrin Adaptor Proteins 1 and 3 in Lipoplex Trafficking |
| title_fullStr |
A New Role for Clathrin Adaptor Proteins 1 and 3 in Lipoplex Trafficking |
| title_full_unstemmed |
A New Role for Clathrin Adaptor Proteins 1 and 3 in Lipoplex Trafficking |
| title_sort |
new role for clathrin adaptor proteins 1 and 3 in lipoplex trafficking |
| description |
Intracellular protein trafficking through secretory and endocytic pathways depends on the function of adaptor proteins that bind motifs on cargo proteins. The adaptor proteins then recruit coat proteins such as clathrin, enabling the formation of a transport vesicle. While studying the role of the clathrin adaptor proteins, AP-1, AP-2 and AP-3 in viral protein trafficking, we discovered that AP-1 and AP-3 potentially have a role in successful transfection of mammalian cells with DNA-liposome complexes (lipoplexes). We showed that AP-1, -2 and -3 are not required for lipoplexes to enter cells, but that lipoplexes and/or released DNA are unable to reach the nucleus in the absence of AP-1 or AP-3, leading to minimal exogenous gene expression. In contrast, gene expression from liposome-delivered mRNA, which does not require nuclear entry, was not impaired by the absence of AP-1 or AP-3. Despite the use of lipoplexes to mediate gene delivery being so widely used in cell biology and, more recently, gene therapy, the mechanism by which lipoplexes or DNA reach the nucleus is poorly characterised. This work sheds light on the components involved in this process, and demonstrates a novel role for AP-1 and AP-3 in trafficking lipoplexes. |
| publisher |
Public Library of Science |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950295/ |
| _version_ |
1612066535176667136 |