title: Morphological change by overexpression of D385A dominant negative presenilin 1 in human neuroblastoma SH-SY5Y cells.
abstract: 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.
authors.affiliation: Department of Neurobiology and 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Daiju
authors.initials: D
authors.lastname: Tsuchiya
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Takata
authors.forename: Takashi
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Kengo
authors.initials: K
authors.lastname: Uemura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miki
authors.forename: Tadaomi
authors.initials: T
authors.lastname: Takenawa
authors.forename: Shun
authors.initials: S
authors.lastname: Shimohama
mesh_terms: 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
chemical_list: D053764:Presenilin-1