BACE1 interacts with lipid raft proteins

• Published in: Journal of neuroscience research Vol. 84; no. 4; pp. 912 - 917
• Main Authors: Hattori, Chinatsu, Asai, Masashi, Onishi, Hayato, Sasagawa, Noboru, Hashimoto, Yasuhiro, Saido, Takaomi C., Maruyama, Kei, Mizutani, Shigehiko, Ishiura, Shoichi
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2006
• Subjects: Alzheimer's disease; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Amyloid Precursor Protein Secretases; APP; Aspartic Acid Endopeptidases; Blotting, Northern; Caveolin 1 - genetics; Caveolin 1 - metabolism; Cell Line; Endopeptidases - genetics; Endopeptidases - metabolism; Gene Expression - physiology; Humans; Immunoprecipitation - methods; lipid rafts; Membrane Microdomains - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - biosynthesis; Subcellular Fractions - metabolism; β-secretase
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.20981

A neuropathological hallmark of Alzheimer's disease is the presence of amyloid plaques in the brain. Amyloid‐β peptide (Aβ) is the major constituent of the plaques and is generated by proteolytic cleavages of amyloid precursor protein (APP) by β‐ and γ‐secretases. Growing evidence shows that lipid rafts are critically involved in regulating the Aβ generation. In support of this, APP, Aβ, and presenilins have been found in lipid rafts. Although cholesterol plays a crucial role in maintaining lipid rafts, functions of other components in the generation of Aβ are unknown. Caveolins (CAVs) and flotillins (FLOTs) are principal proteins related to lipid rafts and have been suggested to be involved in APP processing. Here, we report that FLOT‐1 binds to BACE1 (beta‐site APP cleaving enzyme 1) and that overexpression of CAV‐1 or FLOT‐1 results in recruiting BACE1 into lipid rafts and influence on β‐secretase activity in cultured cells. Our results show that both CAV‐1 and FLOT‐1 may modulate β‐secretase activity by interacting with BACE1. © 2006 Wiley‐Liss, Inc.