Morphological Change by Overexpression of D385A Dominant Negative Presenilin 1 in Human Neuroblastoma SH-SY5Y Cells

Daiju Tsuchiya; Yoshihisa Kitamura; Kazuyuki Takata; Takashi Taniguchi; Kengo Uemura; Hiroaki Miki; Tadaomi Takenawa; Shun Shimohama

Journal of Pharmacological Sciences (Jan 2006)

Morphological Change by Overexpression of D385A Dominant Negative Presenilin 1 in Human Neuroblastoma SH-SY5Y Cells

Daiju Tsuchiya,
Yoshihisa Kitamura,
Kazuyuki Takata,
Takashi Taniguchi,
Kengo Uemura,
Hiroaki Miki,
Tadaomi Takenawa,
Shun Shimohama

Affiliations

Daiju Tsuchiya: Department of Neurobiology and 21st Century COE Program, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Japan
Yoshihisa Kitamura: Department of Neurobiology and 21st Century COE Program, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Japan
Kazuyuki Takata: Department of Neurobiology and 21st Century COE Program, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Japan
Takashi Taniguchi: Department of Neurobiology and 21st Century COE Program, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Japan
Kengo Uemura: Horizontal Medical Research Organization, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan; Department of Neurology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan
Hiroaki Miki: Division of Biochemistry, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
Tadaomi Takenawa: Division of Biochemistry, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
Shun Shimohama: Department of Neurology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan; Corresponding author. Present address for correspondence: Department of Neurology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556, Japan

Journal volume & issue: Vol. 102, no. 3
pp. 354 – 358

Abstract

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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. Keywords:: presenilin 1, SH-SY5Y cell, neuritogenesis

Published in Journal of Pharmacological Sciences

ISSN: 1347-8613 (Print)
Publisher: Elsevier
Country of publisher: Japan
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/journal-of-pharmacological-sciences

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