Low Density Lipoprotein Receptor Related Proteins as Regulators of Neural Stem and Progenitor Cell Function

Figure 1

LRP1 maturation and structure. This schematic depicts the LRP1 precursor protein, which is synthesized in the endoplasmic reticulum and is bound to the chaperone protein, receptor associated protein (RAP). The LRP1 precursor is transported to the trans-Golgi network where the low pH causes RAP to dissociate. The protease Furin cleaves the LRP1 precursor at the RX(K/R)R consensus sequence to generate a large -chain (515 kDa) and a smaller -chain (85 kDa) which are noncovalently linked and shuttled to the cell membrane, where they are embedded as one functional unit. The -chain contains four ligand-binding domains (red) that interact with a large number of ligands. The -chain contains a small extracellular region, a transmembrane region which anchors the LRP1 protein within the plasma membrane, as well as two dileucine (LL, green) motifs and two asparagine-proline-x-tyrosine (NPXY, blue) motifs, where the distal motif is contiguous with a tyrosine-x-x-leucine (YXXL, pink) motif which interact with intracellular adaptor proteins and the endocytotic machinery.