The LDL Receptor Family
More than 10 receptors have now been identified as members of the low-density lipoprotein receptor (LDLR) family; they all contain characteristic ligand-binding repeats, epidermal growth factor-like repeats and propeller-like structures with YWTD motifs.
These receptors bind a diverse array of ligands, including apoE and amyloid precursor protein, to mediate their transport or signaling. A unique feature of LRP1 endocytic trafficking is its rapid endocytosis, which is mediated by several endocytosis signals, including an YXXL motif, a dileucine motif and a protein kinase A-mediated phosphorylation of a serine residue. The lab has also found that a cytosolic adaptor protein, sorting nexin 17, interacts with the first NPXY motif of LRP1 tail and regulates its recycling.
These studies focus on understanding how LDLR family members traffic within cells and how their biological functions are regulated by these trafficking events. In addition to LRP1, the lab is also studying low-density lipoprotein receptor-related protein 1B (LRP1B) and LRP6 trafficking, signaling and functions. LRP1B is a putative tumor suppressor that is highly homologous to LRP1. LRP6 is a co-receptor for canonical Wnt/beta-catenin signaling.
Additionally, the lab is studying how two chaperones, the receptor-associated protein (RAP) and the MESD protein, regulate the complex folding of LDLR family members and their biological functions.