SLC38A2 provides proline to fulfill unique synthetic demands arising during osteoblast differentiation and bone formation.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Shen, L; Yu, Y; Zhou, Y; Pruett-Miller, SM; Zhang, G-F; Karner, CM

Published Date

  • March 9, 2022

Published In

Volume / Issue

  • 11 /

PubMed ID

  • 35261338

Pubmed Central ID

  • PMC9007586

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.76963

Language

  • eng

Conference Location

  • England