BMP-1 disrupts cell adhesion and enhances TGF- β activation through cleavage of the matricellular protein thrombospondin-1.

BMP-1 disrupts cell adhesion and enhances TGF-β activation through cleavage of the matricellular protein thrombospondin-1. Sci Signal. 2020 Jul 07;13(639): Authors: Anastasi C, Rousselle P, Talantikite M, Tessier A, Cluzel C, Bachmann A, Mariano N, Dussoyer M, Alcaraz LB, Fortin L, Aubert A, Delolme F, El Kholti N, Armengaud J, Fournié P, Auxenfans C, Valcourt U, Goff SV, Moali C Abstract Bone morphogenetic protein 1 (BMP-1) is an important metalloproteinase that synchronizes growth factor activation with extracellular matrix assembly during morphogenesis and tissue repair. The mechanisms by which BMP-1 exerts these effects are highly context dependent. Because BMP-1 overexpression induces marked phenotypic changes in two human cell lines (HT1080 and 293-EBNA cells), we investigated how BMP-1 simultaneously affects cell-matrix interactions and growth factor activity in these cells. Increasing BMP-1 led to a loss of cell adhesion that depended on the matricellular glycoprotein thrombospondin-1 (TSP-1). BMP-1 cleaved TSP-1 between the VWFC/procollagen-like domain and the type 1 repeats that mediate several key TSP-1 functions. This cleavage induced the release of TSP-1 C-terminal domains from the extracellular matrix and abolished its previously described multisite cooperative interactions with heparan sulfate proteoglycans and CD36 on HT1080 cells. In addition, BMP-1-dependent proteolysis potentiated the TSP-1-mediated activation of...
Source: Science Signaling - Category: Biomedical Science Authors: Tags: Sci Signal Source Type: research