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J. Biol. Chem., Vol. 281, Issue 42, 31562-31571, October 20, 2006

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The Low Density Lipoprotein Receptor-related Protein Functions as an Endocytic Receptor for Decorin^*

From the 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

Decorin is a small leucine-rich proteoglycan that modulates the activity of transforming growth factor type 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.

Received for publication, March 28, 2006 , and in revised form, July 5, 2006.

^* This work was supported in part FONDAP-Biomedicine Grants 13980001, MDA 3790, and FONDECYT 1020726. The Millennium Institute for Fundamental and Applied Biology is financed in part by the Ministerio de Planificación y Cooperación (Chile). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported in part by an International Research Scholar grant from the Howard Hughes Medical Institute.

² Supported by DIPUC and CONICYT Fellowship AT-24050108.

³ To whom correspondence should be addressed. Tel.: 56-2-6862112; Fax: 56-2-2229995; E-mail: mmarzolo{at}bio.puc.cl.

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