LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way.
Wnt signaling through the canonical beta-catenin pathway plays essential roles in development and disease. Low-density-lipoprotein receptor-related proteins 5 and 6 (Lrp5 and Lrp6) in vertebrates, and their Drosophila ortholog Arrow, are single-span transmembrane proteins that are indispensable for Wnt/beta-catenin signaling, and are likely to act as Wnt co-receptors. This review highlights recent progress and unresolved issues in understanding the function and regulation of Arrow/Lrp5/Lrp6 in Wnt signaling. We discuss Arrow/Lrp5/Lrp6 interactions with Wnt and the Frizzled family of Wnt receptors, and with the intracellular beta-catenin degradation apparatus. We also discuss the regulation of Lrp5/Lrp6 by other extracellular ligands, and LRP5 mutations associated with familial osteoporosis and other disorders.
He
Xi
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Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. xi.he@childrens.harvard.edu
Semenov
Mikhail
M
Tamai
Keiko
K
Zeng
Xin
X
D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D026502:LDL-Receptor Related Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C474373:arr protein, Drosophila; D051176:beta Catenin