Regulated proteolysis of APP and ApoE receptors.
The beta-amyloid precursor protein (APP) shares intracellular and extracellular-binding partners with the family of receptors for apolipoprotein E (apoE). Binding of APP and apoE receptors to specific extracellular matrix proteins (F-spondin and Reelin) promotes their presence on the cell surface and influences whether they will interact with specific cytoplasmic adaptor proteins. Cleavage of APP and apoE receptors at the cell surface occurs by alpha-secretase activities; thus, the processing of these proteins can be regulated by their trafficking either to or from the cell surface. Their cleavages can also be regulated by tissue inhibitor of metalloproteinase-3 (TIMP-3), a metalloprotease inhibitor in the extracellular matrix. ApoE receptors have functions in neuronal migration during development and in proper synaptic function in the adult. Thus, the functions of apoE receptors and by analogy of APP will be modified by the various extracellular and intracellular interactions reviewed in this paper.
Hoe
Hyang-Sook
HS
Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road, NW, Washington, DC 20057-1464, USA.
Rebeck
G William
GW
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D000091042:Reelin Protein; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D000091042:Reelin Protein; D019717:Tissue Inhibitor of Metalloproteinase-3; D010447:Peptide Hydrolases; C000717127:RELN protein, human