Functional interactions of APP with the apoE receptor family.
The beta-amyloid precursor protein (APP) is central to the pathogenesis of Alzheimer's disease, but its normal functions in the brain are poorly understood. A number of APP-interacting proteins have been identified: intracellularly, APP interacts with adaptor proteins through its conserved NPXY domain; extracellularly, APP interacts with a component of the extracellular matrix, F-spondin. Interestingly, many of these APP-interacting proteins also interact with the family of receptors for apolipoprotein E (apoE), the Alzheimer's disease risk factor. apoE receptors also share with APP the fact that they are cleaved by the same secretase activities. apoE receptors are shed from the cell surface, a cleavage that is regulated by receptor-ligand interactions, and C-terminal fragments of apoE receptors are cleaved by gamma-secretase. Functionally, both APP and apoE receptors affect neuronal migration and synapse formation in the brain. This review summarizes these numerous interactions between APP and apoE receptors, which provide clues about the normal functions of APP.
Hoe
Hyang-Sook
HS
Department of Neuroscience, Georgetown University, Washington, District of Columbia 20007, USA.
Rebeck
George William
GW
D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D013569:Synapses / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D016326:Extracellular Matrix Proteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C429104:SPON1 protein, human; D053829:Amyloid Precursor Protein Secretases