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Regulated Proteolysis of APP and ApoE Receptors

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Abstract

The β-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 α-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.

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Abbreviations

APP:

β-amyloid precursor protein

apoE:

apolipoprotein E

TIMP-3:

tissue inhibitor of metalloproteinase-3

AD:

Alzheimer’s disease

CTF:

C-terminal fragment

ADAM:

A disintegrin and metalloproteinase

LDLr:

low-density lipoprotein receptor

VLDLr:

very low-density lipoprotein receptor

ApoEr2:

apoE receptor 2

LRP:

low-density lipoprotein receptor-related protein

ICD:

intracellular domain

PSD:

post-synaptic density

PDZ:

PSD-95/Dlg/ZO-1

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Acknowledgments

This work is supported NIH AG14473 (GWR), NIH AG030060 (GWR), and the Alzheimer’s Research Fund in memory of Bill and Marie Drach.

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  1. Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road, NW, Washington, DC, 20057-1464, USA

    Hyang-Sook Hoe & G. William Rebeck

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  1. Hyang-Sook Hoe
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  2. G. William Rebeck
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Correspondence to G. William Rebeck.

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Hoe, HS., Rebeck, G.W. Regulated Proteolysis of APP and ApoE Receptors. Mol Neurobiol 37, 64–72 (2008). https://doi.org/10.1007/s12035-008-8017-0

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  • DOI: https://doi.org/10.1007/s12035-008-8017-0

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