RT Journal Article
SR Electronic
T1 SLC38A2 provides proline to fulfil unique synthetic demands arising during osteoblast differentiation and bone formation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.12.475981
DO 10.1101/2022.01.12.475981
A1 Leyao Shen
A1 Yilin Yu
A1 Yunji Zhou
A1 Shondra M. Pruett-Miller
A1 Guo-Fang Zhang
A1 Courtney M. Karner
YR 2022
UL http://biorxiv.org/content/early/2022/01/12/2022.01.12.475981.abstract
AB Cellular differentiation is associated with the acquisition of a unique protein signature which 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 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.Competing Interest StatementThe authors have declared no competing interest.