Internalization and intracellular processing of bone morphogenetic protein (BMP) in rat skeletal muscle myoblasts (L6).
Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGF-beta) superfamily capable of inducing bone and cartilage formation in ectopic extraskeletal sites and transducing their effects through binding to serine-threonine kinase receptors. In this study, the fate of 125I-labelled native BMP after binding to cell surface receptors on L6-myoblasts was examined with both continuous and intermittent exposure of the ligand. BMP was readily internalized in L6 cells at +37 degrees C, and the internalization reached a plateau in 2 h. Intracellular degradation of 125I-labelled BMP was established, and degradation products were also detected in binding buffer, indicating exocytosis of the processed ligands. BMP receptors were shown to be subject to acute down-regulation by the ligand, and receptors were completely recycled in 3 h. Hence, we conclude that BMP receptors, like receptors for various other polypeptide ligands, have the ability to mediate intracellular delivery and degradation of the ligand.
Jortikka
L
L
Institute of Medical Technology, University of Tampere, Finland. lj39291@uta.fi
Laitinen
M
M
Lindholm
T S
TS
Marttinen
A
A
D000818:Animals; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D017978:Receptors, Growth Factor
D019485:Bone Morphogenetic Proteins; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D052004:Bone Morphogenetic Protein Receptors