Transglutaminase type 2-dependent selective recruitment of proteins into exosomes under stressful cellular conditions
| Autor: | Federica Rossin, Maria Grazia Farrace, Sara Altuntas, Gian Maria Fimia, Laura Falasca, Manuela D’Eletto, Laura Diaz-Hidalgo, Manuela Antonioli, Claudia Marsella, Mauro Piacentini |
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| Přispěvatelé: | Diaz Hidalgo, Laura, Altuntas, Sara, Rossin, Federica, D'Eletto, Manuela, Marsella, Claudia, Farrace, Maria Grazia, Falasca, Laura, Antonioli, Manuela, Fimia, Gian Maria, Piacentini, Mauro |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
MG132 Huntingtin Leupeptins Cell Cycle Proteins Exosomes Gene Knockout Techniques Mice chemistry.chemical_compound Trinucleotide Repeats ALIX Protein Interaction Mapping TSG101 Cells Cultured Huntingtin Protein BAG3 Transglutaminase type 2 Huntington's disease Cell biology DNA-Binding Proteins Protein Transport Proteasome Endopeptidase Complex Settore BIO/06 Cysteine Proteinase Inhibitors Biology Protein Aggregation Pathological 03 medical and health sciences GTP-Binding Proteins Stress Physiological Animals Humans Protein Glutamine gamma Glutamyltransferase 2 Molecular Biology Adaptor Proteins Signal Transducing Transglutaminases Endosomal Sorting Complexes Required for Transport Calcium-Binding Proteins Cell Biology Fibroblasts Microvesicles Exosome HEK293 Cells 030104 developmental biology Proteostasis Proteasome chemistry Mutation Apoptosis Regulatory Proteins Biogenesis Transcription Factors |
| Popis: | Numerous studies are revealing a role of exosomes in intercellular communication, and growing evidence indicates an important function for these vesicles in the progression and pathogenesis of cancer and neurodegenerative diseases. However, the biogenesis process of exosomes is still unclear. Tissue transglutaminase (TG2) is a multifunctional enzyme with different subcellular localizations. Particularly, under stressful conditions, the enzyme has been also detected in the extracellular matrix, but the mechanism(s) by which TG2 is released outside the cells requires further investigation. Therefore, the goal of the present study was to determine whether exosomes might be a vehicle for TG2 to reach the extracellular space, and whether TG2 could be involved in exosomes biogenesis. To address this issue, we isolated and characterized exosomes derived from cells either expressing or not TG2, under stressful conditions (i.e. proteasome impairment or expressing a mutated form of huntingtin (mHtt) containing 84 polyglutamine repeats). Our results show that TG2 is present in the exosomes only upon proteasome blockade, a condition in which TG2 interacts with TSG101 and ALIX, two key proteins involved in exosome biogenesis. Interestingly, we found that TG2 favours the assembly of a protein complex including mHtt, ALIX, TSG101 and BAG3, a co-chaperone involved in the clearance of mHtt. The formation of this complex is paralleled by the selective recruitment of mHtt and BAG3 in the exosomes derived from TG2 proficient cells only. Overall, our data indicate that TG2 is an important player in the biogenesis of exosomes controlling the selectivity of their cargo under stressful cellular conditions. In addition, these vesicles represent the way by which cells can release TG2 into the extracellular space under proteostasis impairment. |
| Databáze: | OpenAIRE |
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