ALG-2 participates in recovery of cells after plasma membrane damage by electroporation and digitonin treatment

Autor:	Sophie E. B. Ambjørner, S. B. Panina, Martin W. Berchtold, Pernille Winding Gojkovic, Simone M. Jensen, Jonas Bagge, Jonas M. la Cour
Jazyk:	angličtina
Rok vydání:	2018
Předmět:	0301 basic medicine Cell Cell Membranes Cultured tumor cells lcsh:Medicine Mechanical Treatment of Specimens Poultry Cell membrane chemistry.chemical_compound Gene Knockout Techniques Calcium-binding protein Gamefowl lcsh:Science Multidisciplinary Chemistry Electroporation Eukaryota Cell biology Digitonin medicine.anatomical_structure Specimen Disruption Vertebrates Cell lines Hyperexpression Techniques Cellular Structures and Organelles Biological cultures Research Article Cell Binding Cell Physiology Cations Divalent Cell Survival Research and Analysis Methods Cell Line Birds Avian Proteins 03 medical and health sciences medicine Gene Expression and Vector Techniques Animals Humans HeLa cells Molecular Biology Techniques Molecular Biology Molecular Biology Assays and Analysis Techniques Calcium-Binding Proteins Cell Membrane lcsh:R Wild type Organisms Biology and Life Sciences Membrane Proteins Cell Biology Cell cultures 030104 developmental biology Membrane protein Specimen Preparation and Treatment Fowl Cancer cell Amniotes Mutation Calcium lcsh:Q Apoptosis Regulatory Proteins Chickens Cloning
Zdroj:	PLoS ONE, Vol 13, Iss 9, p e0204520 (2018) la Cour, J M, Gojkovic, P W, Ambjorner, S E B, Bagge, J, Jensen, S M, Panina, S & Berchtold, M W 2018, ' ALG-2 participates in recovery of cells after plasma membrane damage by electroporation and digitonin treatment ', PLOS ONE, vol. 13, no. 9, e0204520, pp. 1-13 . https://doi.org/10.1371/journal.pone.0204520 PLoS ONE
ISSN:	1932-6203
Popis:	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.
Databáze:	OpenAIRE
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