Cell Surface amyloid β-protein precursor colocalizes with β1 integrins at substrate contact sites in neural cells

Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 03/1997; 17(3):1004-10.
Source: PubMed


Amyloid beta-protein (A beta), the principal constituent of the senile plaques seen in Alzheimer's disease (AD), is derived by proteolysis from the beta-amyloid precursor protein (beta PP). The distribution and trafficking of cell surface beta PP are of particular interest because some of these molecules are direct precursors of secreted A beta and because the localization of beta PP at the cell surface may be related directly to its physiological functions. Recently, we reported that, in cultured hippocampal neurons, cell surface beta PP is preferentially expressed on axons in a striking discontinuous pattern. In this study, we describe the colocalization of cell surface beta PP and integrins in primary cultured cells. In rat hippocampal neurons, cell surface beta PP was colocalized selectively with alpha 1 beta 1 and alpha 5 beta 1 integrin heterodimers at these characteristic segmental locations. In rat cortical astrocytes, both cell surface beta PP and beta 1 integrin were located at the cell periphery in the "spreading" stage shortly after plating. In "flattened" astrocytes cultured for several days, beta PP was found in punctate deposits called point contacts. In these sites, beta PP was colocalized with alpha 1 beta 1, but not with alpha 5 beta 1 integrin heterodimers, the latter of which were situated at focal contact sites. In both neurons and astrocytes examined after shearing, clathrin and alpha-adaptin were colocalized with beta PP on the surface that directly contacts the substratum. These results are consistent with the putative role of beta PP in cell adhesion and suggests that beta PP either interacts with selected integrins or shares similar cellular machinery to promote cell adhesion.

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    • "One such BACE1 substrate is APP, which has been hypothesized to play a role in neuroprotection [29], cell adhesion [99, 117], neurite outgrowth (reviewed in [104]), synapse formation or maintenance [80], as well as regulating synaptic transmission [43]. APP is transported to the neuronal terminal [52, 97] where it is likely processed by BACE1 and γ-secretase to generate secreted APP ectodomain (APPsβ), APP C-terminal fragment (β-CTF), and Aβ [40, 64, 96, 106, 118]. "
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    • "synaptic plasticity (Ashley et al., 2005; Sabo et al., 2003; Yamazaki et al., 1997). "
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    • "In transfected human neuroblastoma cell line, α5β1 integrin appears to mediate the internalization and degradation of exogenous β-amyloid. When deposition of an insoluble amyloid around the α5β1-expressing cells is reduced, the cells show less apoptosis than the control cells (Matter et al., 1998; Yamazaki et al., 1997). Further studies on integrin such as α4β1 and α5β1 integrins in human brain tissue may provide more insight on the role of integrins in aging and Alzheimer's disease. "
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