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Evidence of γ-secretase complex involved in the regulation of intramembrane proteolysis in Entamoeba histolytica.
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- Additional Information
- Source:
Publisher: Elsevier Country of Publication: Netherlands NLM ID: 9708549 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-0329 (Electronic) Linking ISSN: 13835769 NLM ISO Abbreviation: Parasitol Int Subsets: MEDLINE
- Publication Information:
Original Publication: Amsterdam ; New York : Elsevier, c1997-
- Subject Terms:
- Abstract:
Presenilins (PSNs) are multifunctional membrane proteins involved in signal transduction, lysosomal acidification, and certain physiological processes related to mitochondria. The aspartic protease activity of PSN and the formation of a γ-secretase complex with other subunits such as nicastrin (NCT) are required for the biological functions. Although PSN is widely conserved in eukaryotes, most studies on PSN were conducted in metazoans. Homologous genes for PSN and NCT (EhPSN and EhNCT, respectively) are encoded in the genome of Entamoeba histolytica, however, their functions remain unknown. In this study, we showed that EhPSN and EhNCT form a complex on the cell membrane, demonstrating that the parasite possesses γ-secretase. The predicted structure of EhPSN was similar to the human homolog, demonstrated by the crystal structure, and phylogenetic analysis indicated good conservation between EhPSN and human PSN, supporting the premise that EhPSN functions as a subunit of γ-secretase. By contrast, EhNCT appears to have undergone remarkable structural changes during its evolution. Blue native-polyacrylamide gel electrophoresis combined with western blotting indicated that a 150-kDa single band contains both EhPSN (estimated molecular size: 47-kDa) and EhNCT (64-kDa), suggesting that the complex also contains other unknown components or post-translational modifications. Coimmunoprecipitation from amebic lysates also confirmed that EhPSN and EhNCT formed a complex. Indirect immunofluorescence analysis revealed that the complex localized to the plasma membrane. Moreover, EhPSN exhibited protease activity, which was suppressed by a γ-secretase inhibitor. This is the first report of a γ-secretase complex in protozoan parasites.
Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
- Contributed Indexing:
Keywords: Aspartyl protease; Entamoeba histolytica; Intramembrane-cleaving proteases; Nicastrin; Presenilin; Regulated intramembrane proteolysis; γ-Secretase
- Accession Number:
EC 3.4.- (Amyloid Precursor Protein Secretases)
0 (Protozoan Proteins)
- Publication Date:
Date Created: 20240724 Date Completed: 20240912 Latest Revision: 20240912
- Publication Date:
20240913
- Accession Number:
10.1016/j.parint.2024.102925
- Accession Number:
39048023
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