Abnormal cleavage of APP impairs its functions in cell adhesion and migration |
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Authors: | Baiyang Sheng Bo Song Zhenhuan Zheng Fangfang Zhou Guangyuan Lu Nanming Zhao Xiufang Zhang Yandao Gong |
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Affiliation: | aState Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China |
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Abstract: | Amyloid precursor protein (APP) is expressed ubiquitously but its wrong cleavage only occurs in central nervous system. In this research, overexpression of wild type human APP695 was found to stimulate the adhesion and migration of N2a cells. In the cells co-transfected by familial Alzheimer’s disease (FAD)-linked Swedish mutant of APP695 gene plus E9 deleted presenilin1 gene (N2a/Swe.9), however, this stimulating function was impaired compared to that in the cells co-transfected by Swedish mutant of APP695 gene plus dominant negative mutant of presenilin1 D385A gene (N2a/Swe.385). Furthermore, it was also found that the phosphorylation of FAK Tyr-861 and GSK-3β Ser-9 was reduced in N2a/Swe.Δ9 cells, which can be possibly taken as a reasonable explanation for the underlying mechanism. Our results suggest that impaired cell adhesion and migration induced by abnormal cleavage of APP could contribute to the pathological effects in FAD brain. |
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Keywords: | Amyloid precursor protein (APP) Cell adhesion Cell migration Alzheimer’ s disease |
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