Nicastrin-Like, a Novel Transmembrane Protein from Trypanosoma cruzi Associated to the Flagellar Pocket
Nicastrin (NICT) is a transmembrane protein physically associated with the polytypical aspartyl protease presenilin that plays a vital role in the correct localization and stabilization of presenilin to the membrane-bound γ-secretase complex. This complex is involved in the regulation of a wide range of cellular events, including cell signaling and the regulation of endocytosed membrane proteins for their trafficking and protein processing. Methods: In Trypanosoma cruzi, the causal agent of the Chagas disease, a NICT-like protein (Tc/NICT) was identified with a short C-terminus orthologous to the human protein, a large ectodomain (ECD) with numerous glycosylation sites and a single-core transmembrane domain containing a putative TM-domain (457GSVGA461) important for the γ-secretase complex activity. Results: Using the Spot-synthesis strategy with Chagasic patient sera, five extracellular epitopes were identified and synthetic forms were used to generate rabbit anti-Tc/NICT polyclonal serum that recognized a ~72-kDa molecule in immunoblots of T. cruzi epimastigote extracts. Confocal microscopy suggests that Tc/NICT is localized in the flagellar pocket, which is consistent with data from our previous studies with a T. cruzi presenilin-like protein. Phylogenetically, Tc/NICT was localized within a subgroup with the T. rangeli protein that is clearly detached from the other Trypanosomatidae, such as T. brucei. These results, together with a comparative analysis of the selected peptide sequence regions between the T. cruzi and mammalian proteins, suggest a divergence from the human NICT that might be relevant to Chagas disease pathology. As a whole, our data show that a NICT-like protein is expressed in the infective and replicative stages of T. cruzi and may be considered further evidence for a γ-secretase complex in trypanosomatids.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
Microorganisms - 9(2021), 8 vom: 17. Aug. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lechuga, Guilherme Curty [VerfasserIn] |
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| Links: |
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| Themen: |
γ-secretase |
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| Anmerkungen: |
Date Revised 31.08.2021 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3390/microorganisms9081750 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM329857428 |
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| 100 | 1 | |a Lechuga, Guilherme Curty |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Nicastrin-Like, a Novel Transmembrane Protein from Trypanosoma cruzi Associated to the Flagellar Pocket |
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| 500 | |a Date Revised 31.08.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Nicastrin (NICT) is a transmembrane protein physically associated with the polytypical aspartyl protease presenilin that plays a vital role in the correct localization and stabilization of presenilin to the membrane-bound γ-secretase complex. This complex is involved in the regulation of a wide range of cellular events, including cell signaling and the regulation of endocytosed membrane proteins for their trafficking and protein processing. Methods: In Trypanosoma cruzi, the causal agent of the Chagas disease, a NICT-like protein (Tc/NICT) was identified with a short C-terminus orthologous to the human protein, a large ectodomain (ECD) with numerous glycosylation sites and a single-core transmembrane domain containing a putative TM-domain (457GSVGA461) important for the γ-secretase complex activity. Results: Using the Spot-synthesis strategy with Chagasic patient sera, five extracellular epitopes were identified and synthetic forms were used to generate rabbit anti-Tc/NICT polyclonal serum that recognized a ~72-kDa molecule in immunoblots of T. cruzi epimastigote extracts. Confocal microscopy suggests that Tc/NICT is localized in the flagellar pocket, which is consistent with data from our previous studies with a T. cruzi presenilin-like protein. Phylogenetically, Tc/NICT was localized within a subgroup with the T. rangeli protein that is clearly detached from the other Trypanosomatidae, such as T. brucei. These results, together with a comparative analysis of the selected peptide sequence regions between the T. cruzi and mammalian proteins, suggest a divergence from the human NICT that might be relevant to Chagas disease pathology. As a whole, our data show that a NICT-like protein is expressed in the infective and replicative stages of T. cruzi and may be considered further evidence for a γ-secretase complex in trypanosomatids | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a B-cell epitope | |
| 650 | 4 | |a SPOT synthesis | |
| 650 | 4 | |a Trypanosoma cruzi | |
| 650 | 4 | |a flagellar pocket | |
| 650 | 4 | |a nicastrin | |
| 650 | 4 | |a presenilin | |
| 650 | 4 | |a transmembrane motif | |
| 650 | 4 | |a type I transmembrane glycoprotein | |
| 650 | 4 | |a vesicular trafficking | |
| 650 | 4 | |a γ-secretase | |
| 700 | 1 | |a Napoleão-Pêgo, Paloma |e verfasserin |4 aut | |
| 700 | 1 | |a Gomes, Larissa Rodrigues |e verfasserin |4 aut | |
| 700 | 1 | |a da Matta Durans, Andressa |e verfasserin |4 aut | |
| 700 | 1 | |a Provance, David William |c Jr |e verfasserin |4 aut | |
| 700 | 1 | |a De-Simone, Salvatore Giovanni |e verfasserin |4 aut | |
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