The MEC-2E isoform with a large C-terminal completely rescues the touch sensation defect of C. elegans
Abstract Human podocin and C. elegans MEC-2 belong to the stomatin protein superfamily. They share 49% identity and 91% similarity both in the evolutionary conserved PHB domain (123-284 aa) and in the oligomerization region (273-351 aa). Amino acid substitutions in these conserved regions can modify...
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Nature Portfolio
2025-07-01
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| author | Tália Magdolna Keszthelyi Regina Légrádi Dóra Pálya Tímea Köles Ágnes Regős Dóra Karancsiné Menyhárd Kálmán Tory |
| author_facet | Tália Magdolna Keszthelyi Regina Légrádi Dóra Pálya Tímea Köles Ágnes Regős Dóra Karancsiné Menyhárd Kálmán Tory |
| author_sort | Tália Magdolna Keszthelyi |
| collection | DOAJ |
| description | Abstract Human podocin and C. elegans MEC-2 belong to the stomatin protein superfamily. They share 49% identity and 91% similarity both in the evolutionary conserved PHB domain (123-284 aa) and in the oligomerization region (273-351 aa). Amino acid substitutions in these conserved regions can modify the podocin oligomerization and thus the pathogenicity of trans-associated NPHS2 variants, known as interallelic interactions. The MEC-2A isoform was formerly considered to be the functional isoform and used to evaluate the effect of pathogenic podocin variants. The mec-2 mutant worms are mechanosensation deficient, and, as recently described, also chemosensation deficient. To study the interallelic interactions of podocin in vivo, we aimed to rescue the phenotype of the mec-2 mutant worm by reexpressing podocin (383 aa). However, we did not detect any chemotaxis defects in mec-2(u37) null mutants nor in mec-2(e75) missense mutants. No mechanosensation rescue was achieved by MEC-2A, but with a 17,5 kb genomic region and the MEC-2E isoform (1239 aa) with a large C-terminal. Truncating the last third of the large C-terminal abolished its rescue effect. In conclusion, the function of MEC-2 in mechanosensation requires a large C-terminal encoded by the MEC-2E isoform. Accordingly, human podocin cannot rescue the phenotype of mec-2 mutants. |
| format | Article |
| id | doaj-art-e2f51758946d4227a25cad53281a5238 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-e2f51758946d4227a25cad53281a52382025-08-20T04:03:02ZengNature PortfolioScientific Reports2045-23222025-07-0115111010.1038/s41598-025-10711-wThe MEC-2E isoform with a large C-terminal completely rescues the touch sensation defect of C. elegansTália Magdolna Keszthelyi0Regina Légrádi1Dóra Pálya2Tímea Köles3Ágnes Regős4Dóra Karancsiné Menyhárd5Kálmán Tory6MTA-SE Lendület Nephrogenetic Research GroupMTA-SE Lendület Nephrogenetic Research GroupMTA-SE Lendület Nephrogenetic Research GroupMTA-SE Lendület Nephrogenetic Research GroupMTA-SE Lendület Nephrogenetic Research GroupHUN-REN-ELTE Protein Modeling Research Group, ELTE Eötvös Loránd UniversityMTA-SE Lendület Nephrogenetic Research GroupAbstract Human podocin and C. elegans MEC-2 belong to the stomatin protein superfamily. They share 49% identity and 91% similarity both in the evolutionary conserved PHB domain (123-284 aa) and in the oligomerization region (273-351 aa). Amino acid substitutions in these conserved regions can modify the podocin oligomerization and thus the pathogenicity of trans-associated NPHS2 variants, known as interallelic interactions. The MEC-2A isoform was formerly considered to be the functional isoform and used to evaluate the effect of pathogenic podocin variants. The mec-2 mutant worms are mechanosensation deficient, and, as recently described, also chemosensation deficient. To study the interallelic interactions of podocin in vivo, we aimed to rescue the phenotype of the mec-2 mutant worm by reexpressing podocin (383 aa). However, we did not detect any chemotaxis defects in mec-2(u37) null mutants nor in mec-2(e75) missense mutants. No mechanosensation rescue was achieved by MEC-2A, but with a 17,5 kb genomic region and the MEC-2E isoform (1239 aa) with a large C-terminal. Truncating the last third of the large C-terminal abolished its rescue effect. In conclusion, the function of MEC-2 in mechanosensation requires a large C-terminal encoded by the MEC-2E isoform. Accordingly, human podocin cannot rescue the phenotype of mec-2 mutants.https://doi.org/10.1038/s41598-025-10711-wFunctional transcriptMechanosensationChemotaxisMec-2 |
| spellingShingle | Tália Magdolna Keszthelyi Regina Légrádi Dóra Pálya Tímea Köles Ágnes Regős Dóra Karancsiné Menyhárd Kálmán Tory The MEC-2E isoform with a large C-terminal completely rescues the touch sensation defect of C. elegans Scientific Reports Functional transcript Mechanosensation Chemotaxis Mec-2 |
| title | The MEC-2E isoform with a large C-terminal completely rescues the touch sensation defect of C. elegans |
| title_full | The MEC-2E isoform with a large C-terminal completely rescues the touch sensation defect of C. elegans |
| title_fullStr | The MEC-2E isoform with a large C-terminal completely rescues the touch sensation defect of C. elegans |
| title_full_unstemmed | The MEC-2E isoform with a large C-terminal completely rescues the touch sensation defect of C. elegans |
| title_short | The MEC-2E isoform with a large C-terminal completely rescues the touch sensation defect of C. elegans |
| title_sort | mec 2e isoform with a large c terminal completely rescues the touch sensation defect of c elegans |
| topic | Functional transcript Mechanosensation Chemotaxis Mec-2 |
| url | https://doi.org/10.1038/s41598-025-10711-w |
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