The cytoplasmic domain of the LDL receptor-related protein regulates multiple steps in APP processing
AUTOR(ES)
Pietrzik, Claus U.
FONTE
Oxford University Press
RESUMO
The low-density lipoprotein receptor-related protein (LRP) has recently been implicated in numerous intracellular signaling functions, as well as in Alzheimer’s disease pathogenesis. Studies have shown that the β-amyloid precursor protein (APP) interacts with LRP and that this association may impact the production of amyloid β-protein (Aβ). In this report, we provide evidence that LRP regulates trafficking of intracellular proteins independently of its lipoprotein receptor functions. We show that in the absence of LRP, Aβ production, APP secretion, APP internalization, turnover of full-length APP and stability of APP C-terminal fragments are affected. Importantly, these changes are not APP isoform dependent. Using deletion constructs, the critical region in LRP that modulates APP processing was mapped to a seven peptide domain around the second NPXY domain (residues 4504–4510). Therefore, we propose a model by which LRP functionally modulates APP processing, including those steps critical for Aβ production, through interactions of the cytosolic domains.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=131065Documentos Relacionados
- Proteasome Regulates the Delivery of LDL Receptor-related Protein into the Degradation Pathway
- Modulation of amyloid β-protein clearance and Alzheimer’s disease susceptibility by the LDL receptor–related protein pathway
- Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor–related protein
- 39 kDa receptor-associated protein is an ER resident protein and molecular chaperone for LDL receptor-related protein.
- Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer