Morphological change by overexpression of D385A dominant negative presenilin 1 in human neuroblastoma SH-SY5Y cells.
Presenilin 1 (PS1) is a multifunctional protein, and its mutations are highly related to familial Alzheimer's disease (AD). In this study, we examined the effects of PS1 overexpression on neuronal morphology using SH-SY5Y cells. Overexpression of dominant-negative D385A PS1 induced morphological change and impairment of neurite formation, while those of wild-type and pathogenic P117L mutant PS1 did not change cellular morphology compared with native cells. Moreover, filopodium-formation-related proteins were decreased only in cells overexpressing D385A PS1. Therefore, PS1 may be involved in neuritogenesis and morphological change in SH-SY5Y cells, and P117L mutation may linked to AD by different mechanisms.
Tsuchiya
Daiju
D
Department of Neurobiology and 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto, Japan.
Kitamura
Yoshihisa
Y
Takata
Kazuyuki
K
Taniguchi
Takashi
T
Uemura
Kengo
K
Miki
Hiroaki
H
Takenawa
Tadaomi
T
Shimohama
Shun
S
D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D006801:Humans; D015151:Immunoblotting; D009154:Mutation / Q000502:physiology; D016501:Neurites / Q000502:physiology / Q000648:ultrastructure; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D053764:Presenilin-1 / Q000096:biosynthesis* / Q000235:genetics; D011554:Pseudopodia / Q000502:physiology / Q000648:ultrastructure
D053764:Presenilin-1