ALG-2 participates in recovery of cells after plasma membrane damage by electroporation and digitonin treatment.
The calcium binding protein ALG-2 is upregulated in several types of cancerous tissues and cancer cell death may be a consequence of ALG-2 downregulation. Novel research suggests that ALG-2 is involved in membrane repair mechanisms, in line with several published studies linking ALG-2 to processes o...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC6150531?pdf=render |
| _version_ | 1818152697383092224 |
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| author | Jonas M la Cour Pernille Winding Gojkovic Sophie E B Ambjørner Jonas Bagge Simone M Jensen Svetlana Panina Martin W Berchtold |
| author_facet | Jonas M la Cour Pernille Winding Gojkovic Sophie E B Ambjørner Jonas Bagge Simone M Jensen Svetlana Panina Martin W Berchtold |
| author_sort | Jonas M la Cour |
| collection | DOAJ |
| description | The calcium binding protein ALG-2 is upregulated in several types of cancerous tissues and cancer cell death may be a consequence of ALG-2 downregulation. Novel research suggests that ALG-2 is involved in membrane repair mechanisms, in line with several published studies linking ALG-2 to processes of membrane remodeling and transport, which may contribute to the fitness of cells or protect them from damage. To investigate the involvement of ALG-2 in cell recovery after membrane damage we disrupted the PDCD6 gene encoding the ALG-2 protein in DT-40 cells and exposed them to electroporation. ALG-2 knock-out cells were more sensitive to electroporation as compared to wild type cells. This phenotype could be reversed by reestablishing ALG-2 expression confirming that ALG-2 plays an important role in cell recovery after plasma membrane damage. We found that overexpression of wild type ALG-2 but not a mutated form unable to bind Ca2+ partially protected HeLa cells from digitonin-induced cell death. Further, we were able to inhibit the cell protective function of ALG-2 after digitonin treatment by adding a peptide with the ALG-2 binding sequence of ALIX, which has been proposed to serve as the ALG-2 downstream target in a number of processes including cell membrane repair. Our results suggest that ALG-2 may serve as a novel therapeutic target in combination with membrane damaging interventions. |
| first_indexed | 2024-12-11T13:58:50Z |
| format | Article |
| id | doaj.art-6b0f49f98dfd4383996f07061f2f3797 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T13:58:50Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6b0f49f98dfd4383996f07061f2f37972022-12-22T01:03:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01139e020452010.1371/journal.pone.0204520ALG-2 participates in recovery of cells after plasma membrane damage by electroporation and digitonin treatment.Jonas M la CourPernille Winding GojkovicSophie E B AmbjørnerJonas BaggeSimone M JensenSvetlana PaninaMartin W BerchtoldThe calcium binding protein ALG-2 is upregulated in several types of cancerous tissues and cancer cell death may be a consequence of ALG-2 downregulation. Novel research suggests that ALG-2 is involved in membrane repair mechanisms, in line with several published studies linking ALG-2 to processes of membrane remodeling and transport, which may contribute to the fitness of cells or protect them from damage. To investigate the involvement of ALG-2 in cell recovery after membrane damage we disrupted the PDCD6 gene encoding the ALG-2 protein in DT-40 cells and exposed them to electroporation. ALG-2 knock-out cells were more sensitive to electroporation as compared to wild type cells. This phenotype could be reversed by reestablishing ALG-2 expression confirming that ALG-2 plays an important role in cell recovery after plasma membrane damage. We found that overexpression of wild type ALG-2 but not a mutated form unable to bind Ca2+ partially protected HeLa cells from digitonin-induced cell death. Further, we were able to inhibit the cell protective function of ALG-2 after digitonin treatment by adding a peptide with the ALG-2 binding sequence of ALIX, which has been proposed to serve as the ALG-2 downstream target in a number of processes including cell membrane repair. Our results suggest that ALG-2 may serve as a novel therapeutic target in combination with membrane damaging interventions.http://europepmc.org/articles/PMC6150531?pdf=render |
| spellingShingle | Jonas M la Cour Pernille Winding Gojkovic Sophie E B Ambjørner Jonas Bagge Simone M Jensen Svetlana Panina Martin W Berchtold ALG-2 participates in recovery of cells after plasma membrane damage by electroporation and digitonin treatment. PLoS ONE |
| title | ALG-2 participates in recovery of cells after plasma membrane damage by electroporation and digitonin treatment. |
| title_full | ALG-2 participates in recovery of cells after plasma membrane damage by electroporation and digitonin treatment. |
| title_fullStr | ALG-2 participates in recovery of cells after plasma membrane damage by electroporation and digitonin treatment. |
| title_full_unstemmed | ALG-2 participates in recovery of cells after plasma membrane damage by electroporation and digitonin treatment. |
| title_short | ALG-2 participates in recovery of cells after plasma membrane damage by electroporation and digitonin treatment. |
| title_sort | alg 2 participates in recovery of cells after plasma membrane damage by electroporation and digitonin treatment |
| url | http://europepmc.org/articles/PMC6150531?pdf=render |
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