Cell Surface Amyloid β-Protein Precursor Colocalizes with β1 Integrins at Substrate Contact Sites in Neural Cells

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Abstract
Amyloid β-protein (Aβ), the principal constituent of the senile plaques seen in Alzheimer’s disease (AD), is derived by proteolysis from the β-amyloid precursor protein (βPP). The distribution and trafficking of cell surface βPP are of particular interest because some of these molecules are direct precursors of secreted Aβ and because the localization of βPP at the cell surface may be related directly to its physiological functions. Recently, we reported that, in cultured hippocampal neurons, cell surface βPP is preferentially expressed on axons in a striking discontinuous pattern. In this study, we describe the colocalization of cell surface βPP and integrins in primary cultured cells. In rat hippocampal neurons, cell surface βPP was colocalized selectively with α1β1 and α5β1 integrin heterodimers at these characteristic segmental locations. In rat cortical astrocytes, both cell surface βPP and β1 integrin were located at the cell periphery in the “spreading” stage shortly after plating. In “flattened” astrocytes cultured for several days, βPP was found in punctate deposits called point contacts. In these sites, βPP was colocalized with α1β1, but not with α5β1 integrin heterodimers, the latter of which were situated at focal contact sites. In both neurons and astrocytes examined after shearing, clathrin and α-adaptin were colocalized with βPP on the surface that directly contacts the substratum. These results are consistent with the putative role of βPP in cell adhesion and suggests that βPP either interacts with selected integrins or shares similar cellular machinery to promote cell adhesion.