The hairpin region of WNT7A is sufficient for binding to the Frizzled7 receptor and to elicit signaling in myogenic cells
Wnt signaling is essential for embryonic development and tissue homeostasis. So far, little is known about the importance and functional relevance of the different regions in WNT proteins including regions in their C-terminus identified as hairpin and linker. However, it was shown that the C-terminu...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Computational and Structural Biotechnology Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037022004949 |
| _version_ | 1797978187243716608 |
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| author | Manuel Schmidt Christine Poser Christina Janster Julia von Maltzahn |
| author_facet | Manuel Schmidt Christine Poser Christina Janster Julia von Maltzahn |
| author_sort | Manuel Schmidt |
| collection | DOAJ |
| description | Wnt signaling is essential for embryonic development and tissue homeostasis. So far, little is known about the importance and functional relevance of the different regions in WNT proteins including regions in their C-terminus identified as hairpin and linker. However, it was shown that the C-terminus of WNT7A comprising the linker and the hairpin region is sufficient to elicit signaling. Here, we demonstrate that actually the hairpin region of WNT7A in its C-terminus is fully sufficient to induce non-canonical signaling in myogenic cells while the linker region alone did not show biological activity. Of note, all known non-canonical signaling branches of WNT7A signaling in skeletal muscle were activated by the hairpin region of WNT7A thereby inducing hypertrophy in myotubes, symmetric expansion of satellite stem cells and migration of myoblasts. Furthermore, we demonstrate that the linker region in the C-terminus of WNT7A binds to the FZD7 receptor while it does not activate non-canonical Wnt signaling. However, the hairpin and the linker region of WNT7A can activate canonical Wnt signaling independent of each other suggesting that specificity of downstream signaling might be depending on those specific regions in the C-terminus. |
| first_indexed | 2024-04-11T05:18:59Z |
| format | Article |
| id | doaj.art-e77b415e61584b4a99deeb589d348fc6 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-04-11T05:18:59Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-e77b415e61584b4a99deeb589d348fc62022-12-24T04:55:02ZengElsevierComputational and Structural Biotechnology Journal2001-03702022-01-012063486359The hairpin region of WNT7A is sufficient for binding to the Frizzled7 receptor and to elicit signaling in myogenic cellsManuel Schmidt0Christine Poser1Christina Janster2Julia von Maltzahn3Leibniz Institute on Aging, Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, GermanyLeibniz Institute on Aging, Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, GermanyLeibniz Institute on Aging, Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, GermanyLeibniz Institute on Aging, Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, Germany; Faculty of Health Sciences Brandenburg, Brandenburg University of Technoogy Cottbus-Senftenberg, Germany; Corresponding author.Wnt signaling is essential for embryonic development and tissue homeostasis. So far, little is known about the importance and functional relevance of the different regions in WNT proteins including regions in their C-terminus identified as hairpin and linker. However, it was shown that the C-terminus of WNT7A comprising the linker and the hairpin region is sufficient to elicit signaling. Here, we demonstrate that actually the hairpin region of WNT7A in its C-terminus is fully sufficient to induce non-canonical signaling in myogenic cells while the linker region alone did not show biological activity. Of note, all known non-canonical signaling branches of WNT7A signaling in skeletal muscle were activated by the hairpin region of WNT7A thereby inducing hypertrophy in myotubes, symmetric expansion of satellite stem cells and migration of myoblasts. Furthermore, we demonstrate that the linker region in the C-terminus of WNT7A binds to the FZD7 receptor while it does not activate non-canonical Wnt signaling. However, the hairpin and the linker region of WNT7A can activate canonical Wnt signaling independent of each other suggesting that specificity of downstream signaling might be depending on those specific regions in the C-terminus.http://www.sciencedirect.com/science/article/pii/S2001037022004949Wnt signalingWnt7aHypertrophyMyogenesisSatellite cellMuscle stem cell |
| spellingShingle | Manuel Schmidt Christine Poser Christina Janster Julia von Maltzahn The hairpin region of WNT7A is sufficient for binding to the Frizzled7 receptor and to elicit signaling in myogenic cells Computational and Structural Biotechnology Journal Wnt signaling Wnt7a Hypertrophy Myogenesis Satellite cell Muscle stem cell |
| title | The hairpin region of WNT7A is sufficient for binding to the Frizzled7 receptor and to elicit signaling in myogenic cells |
| title_full | The hairpin region of WNT7A is sufficient for binding to the Frizzled7 receptor and to elicit signaling in myogenic cells |
| title_fullStr | The hairpin region of WNT7A is sufficient for binding to the Frizzled7 receptor and to elicit signaling in myogenic cells |
| title_full_unstemmed | The hairpin region of WNT7A is sufficient for binding to the Frizzled7 receptor and to elicit signaling in myogenic cells |
| title_short | The hairpin region of WNT7A is sufficient for binding to the Frizzled7 receptor and to elicit signaling in myogenic cells |
| title_sort | hairpin region of wnt7a is sufficient for binding to the frizzled7 receptor and to elicit signaling in myogenic cells |
| topic | Wnt signaling Wnt7a Hypertrophy Myogenesis Satellite cell Muscle stem cell |
| url | http://www.sciencedirect.com/science/article/pii/S2001037022004949 |
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