Abnormal cleavage of APP impairs its functions in cell adhesion and migration.
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 big up tri, openE9 deleted presenilin1 gene (N2a/Swe. big up tri, open9), 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-3beta Ser-9 was reduced in N2a/Swe.Delta9 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.
Sheng
Baiyang
B
State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
Song
Bo
B
Zheng
Zhenhuan
Z
Zhou
Fangfang
F
Lu
Guangyuan
G
Zhao
Nanming
N
Zhang
Xiufang
X
Gong
Yandao
Y
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D051379:Mice; D009154:Mutation / Q000235:genetics; D009416:Nerve Regeneration / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3