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

Figure 2

Signalling mechanisms employed by LRP1. (a) The extracellular domain of LRP1 can be shed following cleavage by beta-site APP cleaving enzyme 1 (BACE1) and metalloproteinases (MP) producing a soluble form of LRP1 (sLRP1). The intracellular domain can be cleaved by -secretase and is thought to translocate to the nucleus to influence gene transcription. (b) Ligand binding to LRP1 can result in receptor and ligand internalisation. Once internalised, the ligand/receptor complex can be processed in a multitude of ways, including degradation by lysosomes or resecretion via transcytotic and recycling vesicles. Note that while they are depicted together, ligand and receptor/s are trafficked independently. (c) Specific regions on the intracellular region of LRP1 interact with adaptor proteins such as Disabled-1 (Dab1), which interacts with the NPXY motifs and can recruit nonreceptor tyrosine kinases such as Src and Abl allowing signal transduction. (d) Activation of LRP1 by specific ligands can transactivate other receptors such as tropomyosin receptor kinase A (TrkA), which can then activate downstream signalling pathways to regulate cell function.