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LDL receptor‐related protein (LRP) is an endocytic receptor for decorin and participates in a novel regulatory mechanism of TGFβ signaling by decorin
Author(s) -
CabelloVerrugio Claudio,
Marzolo María Paz,
Brandan Enrique
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1335
Skeletal muscle differentiation is a process strongly inhibited by TGFβ in vitro. Decorin (Dcn), a soluble proteoglycan, can interact with diverse proteins, among them growth factors, extracellular matrix proteins, and cell surface receptors. We have previously demonstrated that myoblast Dcn null clone (Dcn null) shows an accelerated differentiation due to decreased sensitivity to TGFβ. It has been shown that Dcn is internalized by different cell types, although the receptor has not been elucidated. The aim of this work was to understand the mechanism responsible for the decreased sensitivity to TGFβ in Dcn null myoblasts and to determine the endocytic receptor for Dcn. We show that Dcn interacts and is internalized through the LDL receptor‐related protein (LRP). Dcn null myoblasts are less responsive to TGFβ than wild type myoblasts, evaluated by TGFβ dependent p3TPlux reporter activity. This effect is specific for Dcn since Dcn re‐expression restores TGFβ's response to wild type levels. Moreover, we show that in wild type myoblasts RAP (an inhibitor of LRP‐ligand endocytosis) or a specific siRNA to LRP both inhibit p3TPlux activity to the level found in the Dcn null myoblasts. The specificity of this effect is demonstrated by re‐expressing Dcn in Dcn null myoblasts in which RAP and siRNA to LRP both decrease p3TP‐lux activity. Therefore, we demonstrate that LRP is an endocytic receptor for Dcn in myoblasts and Dcn regulates TGFβ signaling in myoblasts through a novel mechanism involving LRP but not Smad‐2 phosphorylation. (Supported by FONDAP, MIFAB, HHMI, CONICYT AT‐24050108)