The low density lipoprotein receptor-related protein functions as an endocytic receptor for decorin.
Decorin is a small leucine-rich proteoglycan that modulates the activity of transforming growth factor type beta and other growth factors and thereby influences the processes of proliferation and differentiation in a wide array of physiological and pathological reactions. Hence, understanding the regulatory mechanisms of decorin activity has broad implications. Here we report that the extracellular levels of decorin are controlled by receptor-mediated catabolism, involving the low density lipoprotein receptor family member, low density lipoprotein receptor-related protein (LRP). We show that decorin is endocytosed and degraded by C2C12 myoblast cells and that both processes are blocked by suppressing LRP expression using short interfering RNA. The same occurs with CHO cells, but not with CHO cells genetically deficient in LRP. Finally, we show that LRP-null CHO cells, transfected to express mini-LRP polypeptides containing either the second or fourth LRP ligand-binding domains, carry out decorin endocytosis and lysosomal degradation. These findings point to LRP-mediated catabolism as a new control pathway for the biological activities of decorin, specifically for its ability to influence extracellular matrix signaling.
Brandan
Enrique
E
Centro de Regulación Celular y Patología Joaquín V. Luco, CRCP, Departamento de Biología Celular y Molecular, MIFAB, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Retamal
Claudio
C
Cabello-Verrugio
Claudio
C
Marzolo
María-Paz
MP
D000818:Animals; D016466:CHO Cells; D002454:Cell Differentiation; D006224:Cricetinae; D058575:Decorin; D004705:Endocytosis / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D007930:Leucine / Q000737:chemistry; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000502:physiology*; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011509:Proteoglycans / Q000737:chemistry* / Q000378:metabolism
C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010455:Peptides; D011509:Proteoglycans; D007930:Leucine