SLC38A2 provides proline to fulfill unique synthetic demands arising during osteoblast differentiation and bone formation
Cellular differentiation is associated with the acquisition of a unique protein signature that is essential to attain the ultimate cellular function and activity of the differentiated cell. This is predicted to result in unique biosynthetic demands that arise during differentiation. Using a bioinfor...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-03-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/76963 |
| _version_ | 1818026232448548864 |
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| author | Leyao Shen Yilin Yu Yunji Zhou Shondra M Pruett-Miller Guo-Fang Zhang Courtney M Karner |
| author_facet | Leyao Shen Yilin Yu Yunji Zhou Shondra M Pruett-Miller Guo-Fang Zhang Courtney M Karner |
| author_sort | Leyao Shen |
| collection | DOAJ |
| description | Cellular differentiation is associated with the acquisition of a unique protein signature that is essential to attain the ultimate cellular function and activity of the differentiated cell. This is predicted to result in unique biosynthetic demands that arise during differentiation. Using a bioinformatic approach, we discovered that osteoblast differentiation is associated with increased demand for the amino acid proline. When compared to other differentiated cells, osteoblast-associated proteins, including RUNX2, OSX, OCN, and COL1A1, are significantly enriched in proline. Using a genetic and metabolomic approach, we demonstrate that the neutral amino acid transporter SLC38A2 acts cell-autonomously to provide proline to facilitate the efficient synthesis of proline-rich osteoblast proteins. Genetic ablation of SLC38A2 in osteoblasts limits both osteoblast differentiation and bone formation in mice. Mechanistically, proline is primarily incorporated into nascent protein with little metabolism observed. Collectively, these data highlight a requirement for proline in fulfilling the unique biosynthetic requirements that arise during osteoblast differentiation and bone formation. |
| first_indexed | 2024-12-10T04:28:44Z |
| format | Article |
| id | doaj.art-edc67b6ea8e5440c940fc0a023481e29 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:28:44Z |
| publishDate | 2022-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-edc67b6ea8e5440c940fc0a023481e292022-12-22T02:02:13ZengeLife Sciences Publications LtdeLife2050-084X2022-03-011110.7554/eLife.76963SLC38A2 provides proline to fulfill unique synthetic demands arising during osteoblast differentiation and bone formationLeyao Shen0https://orcid.org/0000-0002-4952-437XYilin Yu1Yunji Zhou2Shondra M Pruett-Miller3https://orcid.org/0000-0002-3793-585XGuo-Fang Zhang4Courtney M Karner5https://orcid.org/0000-0003-0387-4486Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, United States; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, United StatesDepartment of Cell and Molecular Biology, St. Jude Children’s Research Hospital, Memphis, United StatesSarah W. Stedman Nutrition and Metabolism Center & Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States; Department of Medicine, Duke University School of Medicine, Durham, United StatesDepartment of Orthopaedic Surgery, Duke University School of Medicine, Durham, United States; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States; Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center at Dallas, Dallas, United StatesCellular differentiation is associated with the acquisition of a unique protein signature that is essential to attain the ultimate cellular function and activity of the differentiated cell. This is predicted to result in unique biosynthetic demands that arise during differentiation. Using a bioinformatic approach, we discovered that osteoblast differentiation is associated with increased demand for the amino acid proline. When compared to other differentiated cells, osteoblast-associated proteins, including RUNX2, OSX, OCN, and COL1A1, are significantly enriched in proline. Using a genetic and metabolomic approach, we demonstrate that the neutral amino acid transporter SLC38A2 acts cell-autonomously to provide proline to facilitate the efficient synthesis of proline-rich osteoblast proteins. Genetic ablation of SLC38A2 in osteoblasts limits both osteoblast differentiation and bone formation in mice. Mechanistically, proline is primarily incorporated into nascent protein with little metabolism observed. Collectively, these data highlight a requirement for proline in fulfilling the unique biosynthetic requirements that arise during osteoblast differentiation and bone formation.https://elifesciences.org/articles/76963prolineosteoblastdifferentiationSLC38A2bone development |
| spellingShingle | Leyao Shen Yilin Yu Yunji Zhou Shondra M Pruett-Miller Guo-Fang Zhang Courtney M Karner SLC38A2 provides proline to fulfill unique synthetic demands arising during osteoblast differentiation and bone formation eLife proline osteoblast differentiation SLC38A2 bone development |
| title | SLC38A2 provides proline to fulfill unique synthetic demands arising during osteoblast differentiation and bone formation |
| title_full | SLC38A2 provides proline to fulfill unique synthetic demands arising during osteoblast differentiation and bone formation |
| title_fullStr | SLC38A2 provides proline to fulfill unique synthetic demands arising during osteoblast differentiation and bone formation |
| title_full_unstemmed | SLC38A2 provides proline to fulfill unique synthetic demands arising during osteoblast differentiation and bone formation |
| title_short | SLC38A2 provides proline to fulfill unique synthetic demands arising during osteoblast differentiation and bone formation |
| title_sort | slc38a2 provides proline to fulfill unique synthetic demands arising during osteoblast differentiation and bone formation |
| topic | proline osteoblast differentiation SLC38A2 bone development |
| url | https://elifesciences.org/articles/76963 |
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