Another family of recruiter receptors are the low density lipoprotein (LDL) receptors. LDL receptor and LDL receptor-related proteins (LRP) were initially regarded as endocytosis mediators, but they also recruit downstream molecules such as Disabled-1 (Dab1) and FE65 that are implicated in development (65, 66). Members of the LDL receptor family have been identified in D. melanogaster and C. elegans (67). The cytoplasmic parts of paralogous or orthologous receptors share little sequence similarity with the exception of a short motif that mediates clustering of the LDL receptor in coated pits before endocytosis. Signaling ligands for the LDL receptor family are usually internalized through endocytosis. Because several LDL receptors share common ligands, their function in signaling or endocytosis is mainly determined by their expression pattern (68).
LRPs work in concert with the LDL receptors to mediate the cellular uptake of chylomicron remnants. They also bind structurally diverse and unrelated ligands. Some of the LRPs are scavenger receptors or multiligand receptors (69), each interacting with a large number of ligands and participating in endocytosis and co-receptor functions. As mentioned, LRP5 and LRP6 are also essential for Wnt signaling through the 7TM Frizzled receptor (16, 70).
Relevant reviews and publications:
16. K. I. Pinson, J. Brennan, S. Monkley, B. J. Avery, W. C. Skarnes, An LDL-receptor-related protein mediates Wnt signalling in mice. Nature 407, 535-538 (2000).
65. B. W. Howell, L. M. Lanier, R. Frank, F. B. Gertler, J. A. Cooper, The disabled 1 phosphotyrosine-binding domain binds to the internalization signals of transmembrane glycoproteins and to phospholipids. Mol Cell Biol 19, 5179-5188 (1999).
66. M. M. Hussain, Structural, biochemical and signaling properties of the low-density lipoprotein receptor gene family. Front Biosci 6, D417-428 (2001).
67. B. W. Howell, J. Herz, The LDL receptor gene family: signaling functions during development. Curr Opin Neurobiol 11, 74-81 (2001).
68. J. Gliemann, Receptors of the low density lipoprotein (LDL) receptor family in man. Multiple functions of the large family members via interaction with complex ligands. Biol Chem 379, 951-964 (1998).
69. J. Herz, D. K. Strickland, LRP: a multifunctional scavenger and signaling receptor. J Clin Invest 108, 779-784 (2001).
70. A. Patapoutian, L. F. Reichardt, Roles of Wnt proteins in neural development and maintenance. Curr Opin Neurobiol 10, 392-399 (2000).