TY - JOUR
T1 - The Alzheimer amyloid precursor is associated with the detergent-insoluble cytoskeleton
AU - Refolo, L. M.
AU - Wittenberg, I. S.
AU - Friedrich, V. L.
AU - Robakis, N. K.
PY - 1991
Y1 - 1991
N2 - The amyloid β-protein (AβP), the main component of neuritic plaques in Alzheimer's disease (AD), is derived by unknown mechanisms from a family of amyloid precursor proteins (APPs). Using a detergent extraction procedure, we have found that in brain and in neural cell lines, 50-90% of APP is bound to detergent-insoluble cytoskeleton. Labeling experiments performed in a C6 glioma cell line indicated that both cell surface and intracellular APPs are associated with the cytoskeleton. This association requires intact microtubules and is modulated by protein phosphorylation and by cell density. These findings suggest that the function of cellular APP, presently unknown, involves the cytoskeleton and particularly microtubules. The dynamic nature of the binding and its dependence on microtubules and protein phosphorylation suggest it as a possible target in AD, where abnormal cytoskeletal structures and protein phosphorylation have been reported. Altered cytoskeletal binding of APP might lead to its aberrant proteolysis and generation of the AβP.
AB - The amyloid β-protein (AβP), the main component of neuritic plaques in Alzheimer's disease (AD), is derived by unknown mechanisms from a family of amyloid precursor proteins (APPs). Using a detergent extraction procedure, we have found that in brain and in neural cell lines, 50-90% of APP is bound to detergent-insoluble cytoskeleton. Labeling experiments performed in a C6 glioma cell line indicated that both cell surface and intracellular APPs are associated with the cytoskeleton. This association requires intact microtubules and is modulated by protein phosphorylation and by cell density. These findings suggest that the function of cellular APP, presently unknown, involves the cytoskeleton and particularly microtubules. The dynamic nature of the binding and its dependence on microtubules and protein phosphorylation suggest it as a possible target in AD, where abnormal cytoskeletal structures and protein phosphorylation have been reported. Altered cytoskeletal binding of APP might lead to its aberrant proteolysis and generation of the AβP.
UR - http://www.scopus.com/inward/record.url?scp=0026316233&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.11-12-03888.1991
DO - 10.1523/jneurosci.11-12-03888.1991
M3 - Article
C2 - 1683901
AN - SCOPUS:0026316233
SN - 0270-6474
VL - 11
SP - 3888
EP - 3897
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 12
ER -