Low density lipoprotein receptor-related protein 5, LRP5, is located on the q arm of chromosome 11. More specifically, it is positioned at 13.4.
LRP5 is a transmembrane receptor protein that is located on the cell's surface, specifically mesenchymal progenitor cell which comes from mesenchymal stem cells. LRP5 is a co-receptor withfrizzled-4 receptor protein (from the FZD4 gene) for the Wnt ligand. Together, these two proteins transmit a signal using a Wnt signaling pathway. The pathway functions by allowing the Wnt protein to attach to the frizzled-4, making the Wnt-FZD complex, which then binds to LRP5 and activates the Dishevelled protein (Dvl)(see picture at right). This protein pulls Axin away from the β-catenin destruction complex which means β-catenin does not get destroyed and can thus enter into the nucleus to activate a transcription factor T-cell factor-4 (TCF4). TCF4 activates the transcription for a gene sequence for osteoblastogenesis (the production of bone building cells). If the cell does not need osteoblastogenesis to occur, the pathway can be blocked by the binding of Dickkopf-1 (DKK1) to LRP5 so that instead of turning the cell into a mature osteoblast, the cell is turned into an adipocyte(see picture to the left). The diagram on the right shows that DKK1 inhibits the Wnt receptor by behaving as a non-competitive inhibitor
, after the FZD-Wnt complex binds to LPR5, DKK1 also attaches to LRP5 and turns it off so that the Dishevelled protien cannot function, which means the β-catenin destruction complex is still active. This results in not enough β-catenin entering the nucleus to activate osteoblastogenesis.
Missense Mutations
Van Buchem's Syndrome (home page)
Page Authors: Emmie Ryan and Julie Swihart
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